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“I told myself, ‘I am not going to tolerate that—in my practice, or on a national level or worldwide,’” Dr. McCullough told me. Realizing that COVID had to be fought on multiple fronts, McCullough began contacting physicians in other nations who were reporting success against the disease, including doctors in Italy, Greece, Canada, across Europe, and in Bangladesh and South Africa.

McCullough continues, “If this had been any other form of pneumonia, a respiratory illness, or any other infectious illness in the human body, we know that if we start early, we can actually treat much more easily than wait until patients are very sick.” McCullough says that the rule holds true for COVID-19: “We learned quickly that it takes about two weeks for someone infected with COVID to get sick enough at home to require hospitalization.”

Front-line clinical doctors quickly recognized that the disease was operating through multiple pathways, each requiring their own treatment protocol. “There were three major parts of the illness,” says McCullough: “1) the virus was replicating for as long as two weeks, 2) there was incredible inflammation in the body, and 3) that was followed by blood clotting.” He adds, “By April 2020, most doctors understood a single drug was not going to be enough to treat this illness. We had to use drugs in combination.”

“We quickly developed three principles,” says McCullough; his three-step protocol was as follows:

• Use medications to slow down the virus;

• Use medications to attenuate or reduce inflammation;

• Address blood clotting.

McCullough and his global partners quickly identified a pharmacopoeia of off-the-shelf treatments demonstrating extraordinary efficacy against each stage of COVID when administered early in the course of the disease.

McCullough chronicles the rapid pace with which front-line doctors uncovered rich apothecaries of effective COVID remedies. HHS’s early studies supported hydroxychloroquine’s efficacy against coronavirus since 2005, and by March 2020, doctors from New York to Asia were using it against COVID with extraordinary effect. That month, McCullough and other physicians at his medical center organized, with the FDA, one of the first prophylactic protocols using hydroxychloroquine. “We had terrific data on ivermectin, from the medical teams in Bangladesh and elsewhere by early summer 2020. So now we had two cheap generics.” McCullough and his growing team of 50+ front-line doctors discovered that while HCQ and IVM work well against COVID, adding other medications boosts outcomes drastically. These included azithromycin or doxycycline, zinc, vitamin D, Celebrex, bromhexine, NAC, IV vitamin C, and quercetin. McCullough’s team realized that, like hydroxychloroquine and ivermectin, quercetin—that ubiquitous health store nutraceutical—is an ionophore—meaning that it facilitates zinc uptake in the cells, destroying the capacity of coronavirus to replicate. “The Canadians came on with Colchicine in a high-quality trial based on an initial Greek trial,” McCullough continued. “We learned more from experts at UCLA and elsewhere with respect to blood clotting and the need for aspirin and blood thinners. We got early approval for monoclonal antibodies. It was later learned that both fluvoxamine and famotidine could play roles in multidrug treatment.” LSU Medical School professor Paul Harch discovered peer-reviewed papers from China where researchers there had been using hyperbaric chambers (HBOT) with stunning success.48 Between April and May, a group of NYU researchers reproduced that success by getting patients off ventilators and quickly recovering 18 of 20 ventilator cases using HBOT.49 (Yale is currently conducting Phase 3 with stellar early results.)

There were many other promising treatments. Asian nations were using saline nasal lavages to great effect to reduce viral loads and transmission.50 McCullough discovered he could prophylax patients and drop viral load and prevent transmission with a variety of other oral/nasal rinses and dilute virucidal agents, including povidone iodine, hydrogen peroxide, hypochlorite, and Listerine or mouthwash with cetylpyridinium chloride.Mass General’s infectious disease maven Dr. Michael Callahan had seen hundreds of patients in Wuhan in January 2020, and assessed the impressive efficacy of Pepcid, an over-the-counter indigestion medicine. The Japanese were already using Prednisone, Budesonide, and Famotidine with extraordinary results.

By July 1 [2020], McCullough and his team had developed the first protocol based on signals of benefit and acceptable safety. They submitted the protocol to the American Journal of Medicine. That study, titled “The Pathophysiologic Basis and Clinical Rationale for Early Ambulatory Treatment of COVID-19,”51 quickly became the world’s most-downloaded paper to help doctors treat COVID-19.

“It is extraordinary that Dr. Fauci never published a single treatment protocol before that,” says McCullough, “and that ‘America’s Doctor’ has never, to date, published anything on how to treat a COVID patient. It shocks the conscience that there is still no official protocol. Anyone who tries to publish a new treatment protocol will find themselves airtight blocked by the journals that are all under Fauci’s control.”

The Chinese published their own early treatment protocol on March 3, 2020,52,53 using many of the same categories of prophylactic and early treatment drugs uncovered by McCullough—chloroquine (a cousin of hydroxychloroquine), antibiotics, anti-inflammatories, antihistamines, a variety of steroids, and probiotics to stabilize and fortify the immune system and apothecaries of traditional Chinese medicines, vitamins, and minerals, including a variety of compounds containing quercetin, zinc, and glutathione precursors.54 The Chinese made early treatment the central priority of their COVID strategy. They used intense—and intrusive—track-and-trace surveillance to identify and then immediately hospitalize and treat every COVID-infected Chinese. Early treatment helped the Chinese to end their pandemic by April 2020. “We could have done the same,” says McCullough.

Though now he is often censored, the AMA still lists Dr. McCullough’s study as the most frequently downloaded paper for 2020. The Association of American Physicians and Surgeons (AAPS) downloaded and turned McCullough’s AMA article into its official treatment guide.55 AAPS Director Dr. Jeremy Snavely told me in August 2021 that the Guide had 122,000 downloads: “We figure it has been seen by over a million people. It’s the only trusted guide. Our phone never stops ringing. Mostly the calls are from physicians and patients desperate for the help they cannot get from any HHS website.”

By autumn, front-line physicians had assembled a pharmacopeia of repurposed drugs, all of which were effective against COVID.

By that time, more than 200 studies supported treatment with hydroxychloroquine, and 60 studies supported ivermectin. “We combined these medicines with doxycycline, azithromycin to suppress infection,” says McCullough. Another meta-analysis supported the use of prednisone and hydrocortisone and other widely available steroids to combat inflammation.56 Three studies supported the use of inhaled budesonide against COVID; an Oxford University study published in February 2021 demonstrated that that treatment could reduce hospitalizations by 90 percent in low-risk patients,57 and a publication in April 2021 showed that recovery was faster for high-risk patients, too.58 Furthermore, a very large study supported colchicine as an anti-inflammatory.59 Finally, McCullough’s growing array of physicians had observational data from late-stage treatment of hospitalized patients with full-dose aspirin and antithrombotics, including Enoxaparin, Apixaban, Rivaroxaban, Dabigatran, Edoxaban, and full-dose anticoagulation with low molecular weight heparin for blood clots.60

“We were able to show that doctors can work with four to six drugs in combination, supplemented by vitamins and nutraceuticals including zinc, vitamins D and C, and Quercetin. And they can guide patients at home, even the highest-risk seniors, and avoid a dreaded outcome of hospitalization and death,” said McCullough.

The CIA Dips In Its Toe  

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The CIA had a long, sordid history of secretly promoting the US bioweapons program. One of the agency’s first projects was establishing a network of so-called “ratlines” that Army intelligence officers used to smuggle some 1,600 chemicals and bioweapons and WMD experts—many of them Nazi Party kingpins and notorious war criminals—out of the reach of the Allies’ Nuremberg prosecutors following World War II. The directors of a notorious operation, code-named Paperclip, provided these researchers with new identities and put them to work developing US germ warfare capacity at Ft. Detrick and elsewhere even after 1972. As late as 1997, the CIA defied the Bioweapons Treaty to launch a top-secret—and highly illegal—effort to create a doomsday “bacteria bomblet.”82

The CIA officially made its open debut in the biosecurity racket in 2004, with its launch of Argus, a project that monitors biological, terrorist, and pandemic threats in 178 nations.83 CIA operative and pediatrician Jim Wilson set up the program at Georgetown University with funding from DHS and the Intelligence Innovation Center to create and implement global foreign biological event detection and tracking capability, capable of assessing millions of pieces of information about social behavior daily and to train government officials in pandemic preparedness.84 One of the key figures in this global surveillance effort was CIA officer Dr. Michael Callahan.

Dr. Michael Callahan is one of the biggest names in bioweapons research. Dr. Callahan ran a biosecurity program for the former CIA surrogate USAID before serving as Director of DARPA’s bioweapons research program. At DARPA, he competed to outdo NIH in laundering money through Peter Daszak’s EcoHealth Alliance to perform bioweapons research, including at the Wuhan lab.85

And as DARPA director, Callahan launched the PREDICT project in 2009 following Jeremy Farrar’s fake bird flu pandemic. PREDICT appeared to be a reincarnation of the CIA’s Argus project under the cover of USAID. PREDICT is the largest single source of funding to Daszak, with a $3.4 million subgrant routed through the University of California (2015–2020). PREDICT became the largest funder of gain-of-function studies and served as the principal funding vehicle through which the gain-of-function cartel evaded Barack Obama’s 2014 presidential moratorium.86

When, during the height of the presidential gain-of-function moratorium, Ralph Baric and the UTMB lab’s Vineet Menachery brazenly published their alarming 2015 study—describing their reckless experiments to breed pandemic bat coronaviruses that could spread via respiratory droplets in humanized mice—they omitted mentioning, in their initial online version of the article, that one of the funding sources was USAID-EPT-PREDICT. Apparently hoping to cover its tracks, PREDICT had laundered its grant through Peter Daszak’s EcoHealth Alliance.

USAID’s PREDICT program boasts that it has identified almost a thousand new viruses, including a new strain of Ebola, and trained some 5,000 people. In October 2019, not long before COVID-19 emerged, USAID abruptly ceased funding PREDICT, a decision bemoaned by Daszak in the New York Times as “definitely a loss.”87

Callahan had a chummy relationship with Daszak, with whom he coauthored several articles—including throughout the gain-of-function moratorium. In April 2015, for example, the names of Michael V. Callahan and Peter Daszak appeared as coauthors on a paper published in the Virology Journal and titled “Diversity of Coronavirus in Bats from Eastern Thailand.”88

Callahan was well aware that he and his confederates were toying with fire. In 2005, Callahan testified before Congress as he was moving into his new office at DARPA. He concluded the hearing with a chilling warning about the nation’s new commitment to Janus-faced gain-of-function science that Drs. Fauci, Robert Kadlec, Callahan himself, and many others would proceed to blithely ignore:

the dark science of biological weapon design and manufacture parallels that of the health sciences and the cross mixed disciplines of modern technology. Potential advances in biological weapon lethality will in part be the byproduct of peaceful scientific progress. So, until the time when there are no more terrorists, the US Government and the American people will depend on the scientific leaders of their field to identify any potential dark side aspect to every achievement.89

Even after leaving DARPA and USAID, Callahan periodically boasted of his continuing influence over US pandemic response policies at the highest levels of government. He alluded to his confidence in these mysterious connections in 2012: “I still have federal responsibilities to The White House for pandemic preparedness and exotic disease outbreak which will continue for the near future.”90

On January 4, 2020, Callahan called Dr. Robert Malone from China just as the coronavirus began taking its first wave of casualties. Malone, a former contractor to the US Army Medical Research Institute of Infectious Diseases and the chief medical officer at Alchem Laboratories, is the inventor of the mRNA vaccine technology platform. Malone first met Callahan in 2009 through Malone’s sometime business partner, [Dr. Darrell Ray Galloway (born 1946)], a CIA officer who formerly served in the US Navy and at one point held the post of director of JSTO in the [Defense Threat Reduction Agency, aka "DTRA"]. To Malone, Galloway introduced Callahan as a fellow CIA officer. During his January 4 phone call, Callahan told Malone that he was just outside Wuhan. Malone assumed that Callahan was visiting China under cover of his Harvard and Massachusetts General Hospital appointments. Callahan told Malone that he had been treating “hundreds” of COVID-19 patients. Callahan subsequently described to National Geographic how he had pored through thousands of case studies at the outbreak’s epicenter. He giddily reported his amazement at the virus’s “magnificent infectivity,” and its capacity to explode “like a silent smart bomb in your community.”91 Callahan later confessed to Malone that he lacked authority to be in Wuhan and had escaped by boat when the government imposed its quarantine. Callahan repeated parts of this story to Brendan Borrell, a writer for Science. Later, [DTRA / "Defense Threat Reduction Agency"] scientist [Dr. David Michael Hone (born 1960)], a GS15 officer, warned Malone to stop talking about Callahan, saying that “We had no military personnel in Wuhan at the time of the outbreak and Michael was lying about his presence.” Malone told me, “That would mean that Michael also lied to Brendan Borrell.” On leaving China, Callahan returned to Washington to brief federal officials and then went directly to work as a “special adviser” to Robert Kadlec, managing the government’s response to the coronavirus.

The pharmacy chains Walgreens, Rite Aid and CVS have moved to stop selling the heartburn medicine Zantac and its generic versions after the Food and Drug Administration warned this month that it had detected low levels of a cancer-causing chemical in samples of the drug. 

A Walgreens spokesman said in a statement on Monday that the company had pulled the drug from its shelves “while the FDA continues its review of the products.” A Rite Aid spokesman said the company was “in the process of removing Zantac and generic versions sold under the Rite Aid name from its shelves.”

Walgreens and CVS, which announced its move on Saturday, both noted that the drug, which is known as ranitidine, has not been recalled. The companies said customers who had bought the products could return them for a refund.

The F.D.A. has said it is investigating the source of the contamination as well as the risk to patients, recommending that they talk to their doctors and that those who take over-the-counter versions consider switching to a different medication.

Zantac, the brand-name version of the drug, is sold by Sanofi, but generic versions are widely sold. 

This month, the drug maker Novartis said that its generic-drug division, Sandoz, had stopped distributing a prescription form of ranitidine worldwide while it investigates the F.D.A.’s findings. GlaxoSmithKline has also stopped shipping its generic version of the drug, as well as Dr. Reddy’s Laboratories, a major generic manufacturer. 

The companies, including Sanofi, have stopped short of recalling their products in the United States. In a statement on Monday, Sanofi said that the levels of the contaminant that the F.D.A. had found in “preliminary tests barely exceed amounts found in common foods.”

The company added: “We are working closely with the F.D.A. and are conducting our own robust investigations to ensure we continue to meet the highest quality safety and quality standards.” 

Last week, Apotex, which makes store-branded versions of Zantac for Walgreens, Walmart and Rite-Aid, recalled its ranitidine products.

The European Medicines Agency is also reviewing the drug. Canada has ordered a halt to all distribution of ranitidine while it investigates.

In its warning on Sept. 13, the F.D.A. said that it had found low levels of a cancer-causing contaminant, a type of nitrosamine called nitrosodimethylamine, or NDMA, in the heartburn medications. 

Nitrosamines can cause tumors in the liver and other organs in lab animals, and they are believed to be carcinogenic in humans. NDMA can form during manufacturing if the chemical reactions used to make the drug are not carefully controlled, the F.D.A. has said.

Ranitidine is a histamine blocker that works to lower the acid created in the stomach, according to the F.D.A. The medication is sometimes prescribed to prevent ulcers of the stomach and intestines as well as gastroesophageal reflux disease, the agency says. 

CVS said it would continue to sell other histamine blockers, including Pepcid, Tagamet and the generic equivalents famotidine and cimetidine.

• • • Alarmed by HHS’s inaction, on January 27, 2020, Dr. Bright emailed Dr. Disbrow to complain that Prestige Ameritech’s requests for support to accelerate mask manufacturing “seem[] to be falling on deaf ears.” Understanding that HHS was not taking the necessary steps to prevent a mask shortage, Dr. Bright asked Dr. Disbrow whether BARDA should “put in a budget request to assist.” [12 In BARDA’s initial budget formulation documents, a line item was included to expand domestic mask manufacturing lines. In the various internal discussions with ASPR, ASFR and BARDA, mostly lead by Mr. Shuy, BARDA was told to remove the budget request for mask production, that it purportedly was already covered in the ASPR and SNS budget line.] Id. Later that day, Dr. Falcon emailed Dr. Bright to assure him that her office was “having discussions” about the mask concern. See email from J. Falcon to R. Bright (Jan. 27, 2020), attached hereto as Exhibit 12.
    • Also on January 27, 2020, Dr. Bright received an email from Dr. Larry Kerr, Director of Pandemics and Emerging Threats in HHS Office of Global Affairs, expressing an urgent need to talk about the CDC’s failure to take appropriate actions to respond to the pandemic. See email from L. Kerr to R. Bright (Jan. 27, 2020), attached hereto as Exhibit 13. He stated: “CDC just told the Secretary for his call with Minister Ma that [virus] samples from China are not needed and to de-prioritize it on the upcoming call. We fought back and I think he is still going to raise it but we need BARDA, NIH and FDA to speak up. The USG needs requirement is clear but CDC leadership is not saying that.” Id. Dr. Bright replied that “[w]e cannot emphasize enough the critical need to access virus to initiate MCM development.” See email from R. Bright to L. Kerr (Jan. 27, 2020), attached hereto as Exhibit 14. Dr. Kerr responded that, as of that day, no one had officially asked China for samples. He further noted that Secretary Azar had had a call with China’s Health Minister that morning but did not raise the need for virus samples. [13 According to Dr. Kerr, in the pre-brief before Secretary Azar’s call with the Chinese Health Minister, it was emphatically expressed that BARDA, NIH, and FDA all disagreed with CDC’s position and emphasized to Secretary Azar that there was an urgent need to secure a panel of viruses from China for MCM development.] Dr. Bright expressed disbelief at Secretary Azar’s failure to request virus samples, to which Dr. Kerr replied that “Bob (Kadlec) was on the call but didn’t speak up.” Id.
    • That same morning [of January 27 2020], Dr. Bright participated in a COVID-19 meeting chaired by HHS Deputy Secretary Eric Hargan in Dr. Azar’s absence. During the meeting, Dr. Bright expressed frustration with the slow pace of accessing virus samples and/or clinical specimens from China, which he explained were critical to begin development of vaccines, diagnostics, and medicines. Dr. Bright asked pointedly why the CDC, which was securing viruses from other countries, was delaying providing them to BARDA or to companies to allow for MCM development. Dr. Nancy Messonnier, Director of the National Center for Immunization and Respiratory Diseases (“NCIRD”) at the CDC, who was participating by telephone, responded that Dr. Bright should know better than to make that request because he was well aware that the CDC had agreements with other countries that restricted it from sharing virus specimens with other entities, even within the government. Dr. Bright asked Dr. Messonnier to explain why these restrictions were in place and why BARDA could not use the material to get started on MCM development critical to save American lives. Dr. Messonnier became angry and chastised Dr. Bright, insisting that he “take the topic offline.” [14 Over the next few days, Dr. Bright and his team, at Dr. Bright’s direction, feverishly emailed health officials and laboratories in Australia, Thailand, the United Kingdom and France to try to obtain samples because the CDC had refused to provide information or virus samples to them. It was not even clear to Dr. Bright which virus samples, from the United States or other countries, the CDC actually had because the CDC refused to make this information available to other governmental agencies due its “contractual obligations” to the provider of the samples. Dr. Bright was alarmed by CDC’s insistence that it adhere to contractual obligations that clearly impeded the government’s ability to develop medical counter-measures to save lives.]  Deputy Secretary Hargan, who was observing the conversation play out, gave Dr. Bright a hand signal to stop talking. It was clear to Dr. Bright that his inquiries had created tension.
    • The following day, Dr. Bright sent a note to Dr. Kerr to ask if the daily COVID-19 meetings with Secretary Azar were still occurring. Dr. Kerr confirmed that they were, but explained that due to the “commotion” in the meeting the day before, Judy Stecker, a high-level aide to Secretary Azar, decided that there were too many attendees and cut the list. Later that day, Dr. Bright sent an email to Dr. Kerr noting that he had heard that BARDA had been removed from briefings to Secretary Azar and asked if he had any insights. See email from R. Bright to L. Kerr (Jan. 28, 2020), attached hereto as Exhibit 15. Dr. Kerr responded that the decision to eliminate BARDA was made by Brian Harrison, Secretary Azar’s Chief of Staff, and Ms. Stecker, who decided that only Dr. Kadlec and his chief of staff, Mr. Shuy, who is not a scientist, would be permitted to attend and would present for BARDA. Id. It was obvious that Dr. Bright’s persistent demands for urgent action to respond to the pandemic had caused a “shit storm” and a “commotion” and were unwelcome in the office of the HHS Secretary. As a result, HHS leadership excluded Dr. Bright and BARDA from these recurring meetings and from the critical discussions about addressing the COVID-19 pandemic.

Gilead's antiviral remdesivir is being tested in multiple late-stage studies in China and the US to treat COVID-19.

In the coming weeks, the world will get a sense of whether Gilead Sciences’ remdesivir, an antiviral developed for Ebola, is useful against the novel coronavirus. With the coronavirus pandemic spiraling—during the week of March 23, worldwide infections crossed 500,000 and deaths shot towards 25,000—initial results emerging from several late-stage studies will be under the microscope.

But infectious disease experts on the front lines warn that the data are unlikely to clearly answer the question of whether remdesivir works in COVID-19, the respiratory illness caused by the SARS-CoV-2 virus. Those first tests are in the sickest, hardest-to-treat, patients. Moreover, antivirals don’t have a great track record at taking down coronaviruses, which can be a little more sophisticated than your average RNA virus.

Still, some industry watchers hope the studies signal enough success to convince the US Food and Drug Administration to approve Gilead’s experimental drug.

When a new infectious disease threatens the world, researchers’ first move is to look for any existing therapies that might work against it. As [Sina A Bavari (born 1959)] of Edge Bioinnovation Consulting and Management puts it, when you’re really hungry, you’d rather take a lasagna out of the freezer than make one from scratch. Bavari previously spent many years as chief scientific officer at the US Army Medical Research Institute of Infectious Diseases.

As the coronavirus began to spread, one of the first compounds to be pulled from the freezer was remdesivir. Discovered by Gilead and the Army institute during the 2014 Ebola outbreak in West Africa [see Western African Ebola virus epidemic (2013 - 2016)], the RNA polymerase inhibitor seemed like a sound choice. Although it turned out not to work in Ebola—a failure many blame on how late in the progression of the disease it was given—studies in both healthy and infected people showed the drug is fairly safe.

And researchers point to solid science for why remdesivir might still work against COVID-19.

The SARS-CoV-2 genome is made up of a string of nucleotides that, during replication, are reconstructed, one by one, by the viral polymerase. The RNA-dependent RNA polymerase is a good drug target because it is “almost exclusively associated with the virus,” says University of Wisconsin–Madison virologist Andy Mehle. Polymerase inhibitors will be highly specific for infected cells, sparing healthy ones.

Enter remdesivir, which acts like a mimic for adenosine—one of the nucleotides in that string.

The virus is tricked into incorporating the active form of the drug into its genome, preventing it from making more copies of itself. The mechanism by which remdesivir does that is still unclear, but “polymerase inhibitors primarily work by causing mutations of the genome, or by blocking polymerase function,” Mehle says.

Although Gilead developed remdesivir for Ebola, which belongs to a different family of viruses than SARS-CoV-2, the “viral machinery has elements in common,” Erica Ollmann Saphire, a virus expert at the La Jolla Institute for Immunology, said in an email. Those common elements include polymerases, meaning that for any “safe, bioavailable and manufacturable molecule, the only remaining question is will it work against this other virus,” she said.

While remdesivir was being tested in people with Ebola, several academic and government groups were exploring its potential to take down other viruses, including the coronaviruses that cause SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). They showed in both lab experiments and animal studies that remdesivir could treat infections and prevent them altogether—what scientists call prophylaxis.

In fact, remdesivir is one of only two highly effective compounds to come out of six years of screening against coronaviruses, says [Dr. Mark Randall Denison (born 1956)], a coronavirus expert and director of the Division of Infectious Diseases at Vanderbilt University Medical Center. Denison has collaborated with labs at the University of North Carolina and elsewhere to find small molecules that keep coronaviruses from replicating—and still work if the virus mutates. The other effective compound, EIDD-2801, was discovered by Emory University chemists and recently licensed to Ridgeback Biotherapeutics.

One reason so many compounds failed is that coronaviruses are a little smarter than other RNA viruses. They’re the only ones with a polymerase that can fix errors in their genomes, meaning they can spot and ignore the mimics that drug hunters typically design. [Dr. Mark Randall Denison (born 1956)]'s lab found that remdesivir, like EIDD-2801, can bypass that proofreading function.

Those studies, combined with the Ebola safety data, provided a rationale for trying the compound against the new coronavirus.

At the moment, five Phase III studies are testing the drug against COVID-19. Two began in China in early February—one in people with severe disease, the other in those with mild to moderate disease. One is a US National Institutes of Health–led study that started in February to test the drug in anyone hospitalized with evidence of lung involvement. And two are Gilead-led studies that started in March—one in severe disease and the other in moderate disease.

The first data should come from the studies in China, followed quickly by an initial report from Gilead. With so much pressure to find a COVID-19 treatment—even a modestly effective one—the results will be closely scrutinized. But many on the front lines caution that, even though the studies were carefully designed, the answers might not be clear cut.

“I don’t think the ongoing trials will tell us a lot,” says H. Clifford Lane, clinical director at the National Institutes of Allergy and Infectious Diseases, who is overseeing ongoing studies at the NIH, including its remdesivir study. “The studies might give us some hint, but I do think it will be important to get a study launched that focuses on early disease”—before it becomes severe.

A likely scenario is that several studies “don’t reach statistical significance but show a similar result, and that might be enough to say we should probably be using this,” Lane says. “It’s really hard to know what to do.”

Libby Hohmann, associate professor of medicine and infectious diseases at Massachusetts General Hospital, is similarly cautious. “It’s going to be a challenge to review the data because the protocol allows a wide range of illness into it,” says Hohmann, who leads the hospital’s participation in NIAID’s remdesivir trial. “Unless it’s sort of a home run, it may be difficult to parse at the get go.” 

One issue is that the first studies to read out are the ones focused on the most severe cases, people whose disease might have progressed past the point of help by an antiviral.

“Everything we do in infectious disease is better treated when it’s early on and the bacterial or viral burden and the damage done is lesser,” Hohmann says. Doctors are realizing that COVID-19 is a two-phase illness, she says, that starts with upper respiratory symptoms that worsen after a week to two weeks. At some point during that period, patients “fall of a cliff,” Hohmann notes. “There’s a lot of data and speculation that it’s a kind of immunological phenomenon,” where certain people’s immune or inflammatory response goes awry.

So if those first data in severe or even moderate cases are unclear, it doesn’t necessarily mean the drug doesn’t work. Rather, it could just mean it isn’t being given early enough.

But even if patients are treated early, the benefits could be minimal, Lane warns. Consider, for example, the limitations of Tamiflu (oseltamivir), a common treatment for another virus, influenza. To have any effect, the drug must be taken within 48 hours of symptoms appearing. And even then, “the overall impact on clinical outcomes is not very dramatic,” Lane says. “We don’t have a lot of success in treating RNA viruses.”

In the ideal scenario where the trials do look good, caveats still abound. Ideally, doctors would deploy the drug either prophylactically or just after exposure, but before symptoms appear. Edge Bioinnovation’s Bavari calls it “something to give before you actually go to the hospital so you don’t end up in the hospital.” 

But remdesivir can only be given intravenously, so “it’s not like we’re going to be able to give it to people with the sniffles out in the real world,” Hohmann says.

Nonetheless, her team has been trying to enroll people with a better chance of responding to the drug. Among the 16 patients her clinic has signed up so far, she’s emphasized younger people and those with mild to moderate disease—the ones with shortness of breath rather than those being intubated in the emergency room. “I think we will be able to tell if we’re making a difference in those people,” Hohmann adds.

Gilead says it has no plans to turn remdesivir into a pill. “Based on our understanding of remdesivir from preclinical studies, intravenous administration allows for the most stability and appropriate levels of the drug in the blood system,” a company spokesperson tells C&EN.

Another roadblock is manufacturing. Gilead’s spokesperson notes that “there are currently limited available clinical supplies of remdesivir, but we are working to increase our available supply as rapidly as possible.” For example, the firm is beginning in-house manufacturing of the drug, which had been made only by contract manufacturers. The biotech firm has also added new manufacturing partners around the world to enhance sourcing of everything from raw materials to the finished drug.

Despite the many caveats attached to remdesivir, stock analysts who cover Gilead say it has a reasonable chance of reaching the market. “No one expects it to be a magic bullet,” says Piper Sandler analyst Tyler Van Buren. “But if it works at all in a portion of patients, especially in severe ones, that is very meaningful.” If remdesivir can reduce the need for ventilators or time on supplemental oxygen, Van Buren argues, it could alleviate burden on the healthcare system.

While the FDA approval process typically takes 6–12 months, “this is an unprecedented, once-in-a-century situation,” Van Buren says. Gilead has been submitting as much data as possible to regulatory agencies to expedite approval, he notes. “If the data does look good, there will be tremendous pressure for FDA to make a decision within days.” 

If that happens, could the world end some of the more extreme social distancing measures and start getting back to business? “I think it will depend on the level of efficacy,” NIAID’s Lane says. “The goal remains to prevent the spread of infection. While an effective therapy might have some effect, I doubt it would have a major impact.”

Even in the best-case scenario, where remdesivir moves the needle for patients in a meaningful way, successful deployment will require a health care workforce capable of administering it. Because of shortages of personal protective equipment (PPE) and other supplies, Mass General’s Hohmann says, conditions are already difficult—and the worst is yet to come.

“It’s just a challenge because the clinical workforce is overworked, nervous, worried about their own health, worried about the lack of PPE, and about the tsunami of patients that’s coming,” she says. “If we had all the PPE we need, such that nobody had to worry about going into the room of a patient with known disease, life would be a lot easier around here.”

II. Since 2017, Dr. Bright Has Objected to HHS Leadership’s Cronyism and Award of Contracts to Companies with Political Connections to the Administration.

• BARDA, which is part of the HHS Office of the Assistant Secretary for Preparedness and Response (“ASPR”), was established in 2006 to assist in protecting the nation from bioterrorism, pandemic influenza, and emerging infectious diseases. BARDA supports the development and procurement of medical countermeasures against an array of threats to national security and the public health and acquires medical countermeasures (“MCMs”) in late stage development for the Strategic National Stockpile (“SNS”), the United States’ national repository of antibiotics, vaccines, and other critical medical supplies. BARDA oversees and executes government contracts and acquisitions with a cumulative value approaching $50 billion, and its average annual budget exceeds $1.5 billion.
• BARDA achieves its mission by partnering with private industry. It provides funding, technical assistance, and services, including clinical research and manufacturing support, to facilitate and accelerate the research and development of essential drugs, vaccines, and diagnostics. A company that contracts with BARDA receives not only money, but also a wealth of expertise. BARDA’s subject matter experts work with industry partners to troubleshoot issues, identify and mitigate risks, and achieve FDA approval. BARDA works primarily with drugs and technologies that have completed Phase 1 clinical trials and passed basic safety testing. While NIH generally supports companies through Phase 1 clinical trials, BARDA’s funding and expertise bridge the “valley of death” between Phase 1 clinical trials and FDA approval. [In exceptional situations, including during the ongoing t COVID-19 health crisis, BARDA has flexibility to work with NIH to support drugs and technology that have not yet completed Phase 1 clinical trials. BARDA can give small awards and/or clinical expertise to companies working on compelling solutions that NIH lacks the capacity to support.] BARDA has a unique and impressive track record, as 54 BARDA-supported products to date have achieved FDA approval and are either in the SNS or in the marketplace. [When BARDA was created, it was expected that, given the difficulty of achieving FDA approval, [...]
• Pursuant to BARDA Standard Operating Procedures, the agency solicits proposals by posting either a Request for Proposals (“RFP”), which seeks a specific kind of product, or a Broad Agency Announcement (“BAA”), an open-ended call for more innovative solutions. A BARDA contract officer (“CO”) reviews proposals submitted in response to an RFP or “white papers” submitted in response to a BAA, and passes along to a contract officer representative (“COR”) those submissions that comply with the relevant solicitation requirements. The COR then assembles a Technical Evaluation Panel (“TEP”) to review the submissions. TEPs generally consist of the reviewing CO and COR, as well as subject matter experts from BARDA, NIH, CDC, FDA, and the Department of Defense (“DOD”). TEPs review submissions and evaluate them based solely on scientific merit. They also rank the proposals submitted in response to an RFP. TEPs may request that companies provide additional information, or that authors of white papers submit formal proposals.
• Importantly, BARDA may not consider the financial and business components of a proposal until after the TEP determines that the proposal has scientific merit. If a TEP recommends that BARDA accept a proposal, then a separate group consisting of some members of the TEP and others with budgetary experience reviews the budgetary aspects of the proposal and performs an Independent Government Cost Estimate (“IGCE”). The CO and COR then negotiate the budget and the final details of the work plan with the partner company and, if negotiations are successful, the COR and CO brief the Source Selection Authority (“SSA”), an individual who is authorized to approve the final contract.
• Dr. Bright occasionally served as SSA but typically, and for all COVID-19 related proposals, the SSA was either Deputy Assistant Secretary and Director of Medical Countermeasures Programs Dr. Gary Disbrow, who reported to Dr. Bright, or Director of Influenza and Emerging Infectious Diseases Division Dr. Robert Johnson, who reported to Dr. Disbrow. Generally, Dr. Bright first became involved with a potential contract award after the SSA had decided to award a contract.
• After a contract was approved, Dr. Bright was briefed on it and would often seek additional information on the relevant data, budget, challenges, timelines, and next steps. Dr. Bright was aware of every contract awarded by BARDA, but he did not have the authority, nor did he seek the authority, to award contracts and disperse BARDA funds unilaterally. Every contract is reviewed by a panel of scientific experts, typically from across HHS, and every contract passes through several layers of review before obtaining approval. Indeed, the review process is carefully monitored by various executives, as well as attorneys, in BARDA, ASPR and HHS. The focus of this rigorous review process is scientific merit, and the process is designed to allow no room for industry lobbyists, political influence, or special interests. Under Dr. Bright’s leadership as BARDA Director, contracts were to be awarded solely on the basis of scientific merit, best value for the government’s money, and the potential to keep Americans healthy and safe. [...]
• Despite this rigorous multi-level review process to ensure that BARDA prioritizes public health considerations and makes decisions based exclusively on scientific merit, from approximately the spring of 2017 through the date of his involuntary removal as Director of BARDA, HHS leadership pressured Dr. Bright and BARDA to ignore expert recommendations and instead to award lucrative contracts based on political connections and cronyism. Dr. Bright repeatedly clashed with Dr. Kadlec and other HHS leaders about the outsized role played by John Clerici, an industry consultant to pharmaceutical companies with a longstanding connection to Dr. Kadlec, in the award of government contracts.
• As described in Section A, below, in the summer of 2017, Dr. Bright objected to the efforts of ASPR staff and Mr. Clerici to pressure Dr. Bright to extend a contract with Mr. Clerici’s client, Aeolus Pharmaceuticals (“Aeolus”), which an IPR had concluded should be allowed to expire without further funding. In attempting to justify the extension of this failed contract, Mr. Clerici emphasized that Aeolus’s Chief Executive Officer was a “wildcard” and a friend of Jared Kushner, President Trump’s son-in-law and a Senior Advisor to the President. Dr. Bright stood his ground on this contract, which led to some discord between him and HHS leadership. As discussed in Section B, below, Dr. Bright’s relationship with Dr. Kadlec and other HHS leaders became further strained in late 2018 after Dr. Bright objected to directions from Dr. Kadlec and his Chief of Staff, Christopher Meekins, to transfer $40 million from BARDA to the SNS to allow it to purchase generic Oseltamivir, a drug which a task force of experts had concluded was an inferior choice, in terms of scientific merit and public health preparedness, for the SNS compared to a competing drug developed and recently approved by the FDA. Dr. Kadlec ignored the objections of Dr. Bright and other experts and used BARDA funds to award a lucrative contract to purchase the inferior option, Oseltamivir, from the pharmaceutical company Alvogen, which was one of Mr. Clerici’s clients. As discussed in Section C, below, Dr. Bright also clashed with Dr. Kadlec and other members of HHS leadership when BARDA recommended awarding a task order on a contract only to Amgen to supply a drug for the SNS to treat radiation exposure rather than to both Amgen and Partner Therapeutics. Partner Therapeutics hired Mr. Clerici to manage its bid protest. Dr. Bright became so concerned about the improper role consultants such as Mr. Clerici played in promoting Partner Therapeutics’s drug and their improper influence on Dr. Kadlec and HHS leaders that he requested that the HHS Office of General Counsel (“OGC”) initiate a procurement integrity violation investigation into the matter, and further that the OGC request an investigation by the Inspector General (“IG”) into outside influence on this contract. Dr. Bright subsequently learned that ASPR awarded a $55 million sole source contract to Partner Therapeutics, contrary to the original TEP decision.
• As discussed in Section D, below, the pressure on Dr. Bright escalated in the fall of 2019, after he rejected pressure by Dr. Kadlec to invest millions of dollars in EIDD-2801, a drug developed at Emory University by a longtime friend of Dr. Kadlec. EIDD-2081 was presented as a “miracle cure” for influenza, Ebola and nearly every other virus, even though the developer had not yet conducted clinical trials and no data had been compiled to demonstrate either the efficacy or safety of the drug in humans. Dr. Bright’s reluctance to fund EIDD-2801, which had already receiving $30 million of government funding through NIH and DOD to conduct Phase 1 clinical trials, clearly frustrated Dr. Kadlec and further strained their relationship. Finally, as discussed in Section E below, Dr. Kadlec’s frustration with and animus towards Dr. Bright reached its breaking point when, after the emergence of COVID-19, Dr. Bright resisted efforts to fall into line with the Administration’s directive to promote the broad use of chloroquine and hydroxychloroquine and to award lucrative contracts for these and other drugs even though they lacked scientific merit and had not received prior scientific vetting. Dr. Bright’s refusal to do so, along with his communication with members of Congress, the White House, and the press about these issues, which revealed HHS leadership to be disengaged and dismissive of the emerging threat, proved to be Dr. Bright’s undoing.
• A. ASPR Staff and John Clerici, an industry consultant and friend of Dr. Kadlec, exerted undue pressure on Dr. Bright to improperly extend a contract with Mr. Clerici’s client, Aeolus Pharmaceuticals.
  • • [Full complaint available at Dr. Rick Arthur Bright (born 1966) ]
• B. Over Dr. Bright’s objections, ASPR ignored expert recommendations and used BARDA funds to award contracts to Alvogen, one of Mr. Clerici’s clients.
  • • [Full complaint available at Dr. Rick Arthur Bright (born 1966) ]
• C. ASPR overruled subject matter experts to award a lucrative contract to Partner Therapeutics, one of Mr. Clerici’s clients.
  • • Prior to 2018, BARDA had contracts with Sanofi-Aventis (contract transferred to Partner Therapeutics in 2017) and Amgen for similar drugs to treat radiation exposure. In June 2018, BARDA sought to exercise its option to procure more of the drug(s) for the SNS inventory, and it invited both companies to submit proposals. A panel of subject matter experts that included BARDA and SNS staff reviewed the proposals and recommended that an award be made to Amgen, and not to Partner Therapeutics. BARDA notified Partner Therapeutics of the decision in September 2018. Thereafter, Partner Therapeutics filed a bid protest, which the Government Accountability Office (“GAO”) dismissed on October 25, 2018, determining that the process had been fair.
    • Partner Therapeutics had hired Mr. Clerici to represent the company through the bid protest. Throughout the protest and subsequent proceedings, Mr. Clerici was in regular communication with Dr. Kadlec and his Chiefs of Staff, Mr. Meekins and Bryan Shuy, advocating that BARDA reverse its decision and exercise its option with Partner Therapeutics. The improper influence then trickled down to BARDA, when Dr. Kadlec, Mr. Meekins, and Mr. Shuy repeated Mr. Clerici’s talking points in favor of Partner Therapeutics to Dr. Bright. On several occasions, Mr. Meekins, Mr. Shuy and Dr. Kadlec called Dr. Bright into the ASPR office to share their “scientific” opinions and to try to convince him that the Partner Therapeutics drug was superior to the Amgen drug. They represented that a purchase from Partner Therapeutics was “critical,” because the company was having financial difficulties, and that BARDA should consider strategies to support the company. In both December 2018 and January 2019, Mr. Clerici contacted Dr. Bright to promote the Partner Therapeutics drug and denigrate the Amgen drug. Dr. Bright observed that Mr. Clerici’s talking points mirrored what he heard from ASPR staff, suggesting that they had been talking and coordinating their efforts.
    • At Dr. Bright’s direction, in late 2018, the HHS Office of General Counsel (“OGC”) initiated a procurement integrity investigation about the Partner Therapeutics proposal. In late summer 2018, Dr. Bright had learned that a senior BARDA employee had left and gone to work as a consultant for Partner Therapeutics. BARDA staff had observed that the Partner Therapeutics proposal was suspiciously aligned with BARDA’s internal considerations, consistent with the possibility that Partner Therapeutics had knowledge of BARDA’s internal process. The OGC investigation exposed involvement between the departing employee and Mr. Clerici, who was also working on behalf of Partner Therapeutics. Dr. Bright and his deputy, Dr. Disbrow, attended meetings with OGC attorneys and other HHS officials to address the potential violation and the bid protest, and if necessary, to take corrective actions. In the course of the investigation, it became clear that the primary source of improper communication about BARDA’s internal deliberations was Mr. Clerici, who had been in frequent contact with Dr. Kadlec, Mr. Shuy, and Mr. Meekins.
    • During these meetings, Dr. Bright was vocal about his concerns regarding the inappropriate and possibly illegal communications between Mr. Clerici, Dr. Kadlec, Mr. Shuy, and Mr. Meekins. He also suggested that investigators inspect their phone records to search for evidence of their communications throughout the protest process. Dr. Bright even called for an investigation by the Inspector General (“IG”) to help break up the “cottage industry” of marketing consultants and political influence into these contracts. He emphasized that taxpayer dollars should go to lifesaving medicines, not marketing consultants. Dr. Bright was assured that after the procurement integrity issue was resolved, an IG investigation would commence, although he has no reason to believe it did. Instead, following his call for an IG investigation into Mr. Clerici and Dr. Kadlec’s activities, Dr. Bright was excluded from all subsequent meetings involving the procurement integrity investigation and the resolution of this complaint.
    • After the investigation process was complete, Dr. Bright learned that Dr. Kadlec decided to award a sole source contract to Partner Therapeutics on the basis of industrial mobilization – i.e., the urgent need to keep a company financially viable. [7 As a general matter, it is important to have more than one company in the supply chain able to make a particular drug in case need increases significantly or one company goes out of business. In this case, no such concern actually existed, as there were already three companies that produced similar radiation drugs, and generic equivalence could come soon, which would result in additional options.] In September 2019, the ASPR awarded a contract to Partner Therapeutics for $55 million, overruling the TEP’s recommendation not to exercise the option on its prior contract. Dr. Bright, Dr. Disbrow, and Deputy Director of Detection, Diagnostics and Devices Infrastructure Division Dr. Mary Homer, the COR on the Amgen and Partner Therapeutic contracts, all objected to the ASPR’s decision, but understood that ASPR had the authority to make a final determination that bound BARDA. Additionally, ASPR instructed the SNS to buy the drug exclusively from Partner Therapeutics to prevent the company from becoming bankrupt.
    • Even though Dr. Bright was cut off from the investigation and its conclusion, he took action to decrease future procurement integrity violations within BARDA. Dr. Bright directed his other Deputy Director, Dr. Linda Lambert, to work with the OGC to create a mandatory, two-session training program on procurement integrity for all BARDA employees. Also at Dr. Bright’s direction, Dr. Lambert and OGC developed and implemented a BARDA-wide organizational conflict of interest program, to thoroughly vet every existing and future BARDA contractor for any potential conflict of interest, and to implement processes to vet and train any new contract employees. [...]
• D. Dr. Bright resisted pressure from ASPR to fund a drug touted by Mr. Clerici and his client that lacked scientific merit.
  • • On November 1, 2019, Dr. Kadlec held a meeting with Dr. Bright, Dr. Disbrow, Mr. Clerici, ASPR Senior Science Advisor Dr. David (Chris) Hassell, and Dr. George Painter, Director of the Emory Institute for Drug Development and President and Chief Executive Officer of Drug Innovation Ventures at Emory (“Emory”). During the meeting, Dr. Painter and Mr. Clerici presented a drug, EIDD-2801, as a “cure all” for influenza, Ebola, and nearly every other virus. They requested that BARDA urgently invest millions of dollars into their “miracle cure.” Emory’s presentation included limited data, and no data at all from human trials. Dr. Bright asked targeted questions to understand the science behind the drug and its potential to safely treat patients. Dr. Bright knew that similar experimental drugs in this class had been shown to cause reproductive toxicity in animals, and offspring from treated animals had been born without teeth and without parts of their skulls. Dr. Bright accordingly asked Dr. Painter and Mr. Clerici about clinical trials, including whether Emory had conducted a reproductive study for toxicity, which they had not.
    • Even before the presentation began, Dr. Kadlec indicated his enthusiasm for EIDD-2801’s potential. Observing Dr. Bright’s skepticism during the presentation, Dr. Kadlec asked him why he was not similarly excited. Dr. Bright responded that he was excited about the potential of any promising new drug, but he knew that similar drugs produced fetal abnormalities, and his priority was to ensure drug safety. Unwilling to support a potentially toxic and harmful drug without further data, Dr. Bright asked when Emory planned to begin a clinical study. Dr. Painter and Mr. Clerici responded that Emory had already received $30 million in government funding from NIH and DOD to fund a clinical trial. Because Emory already had government money to fund toxicity studies and initial clinical trials, Dr. Bright suggested that Emory complete these studies and then, once it had amassed evidence that the drug was safe, return to BARDA to discuss funding. Dr. Bright noted that BARDA would then be able to make an informed decision based on scientific data. Dr. Painter countered that Emory needed BARDA funding to start manufacturing as soon as possible. He insisted that EIDD-2801 could be a great asset to American national security, and warned that if BARDA did not fund its manufacturing immediately, Emory would take the drug to another country to manufacture it. Dr. Bright asked where the drug was currently produced. Dr. Painter sheepishly admitted that it was made in China. Dr. Bright insisted that BARDA needed evidence that EIDD-2801was safe in humans before it could consider funding manufacture of the drug.
    • It was clear during the meeting that Dr. Kadlec was extremely unhappy with Dr. Bright’s reluctance to fund this drug immediately without further scientific study. Mr. Clerici, Dr. Painter, and Dr. Kadlec all advocated for immediate funding from BARDA, but Dr. Bright continued to insist on clinical testing, as was standard and proper procedure to ensure safety. Discussing the meeting afterwards, Dr. Disbrow remarked to Dr. Bright, “Wow, you really pushed back.” Nevertheless, following that meeting, Dr. Kadlec repeatedly called Dr. Disbrow and Dr. Bright to ask whether BARDA was going to support EIDD-2801. He also brought EIDD-2801 up in various staff meetings, asking Dr. Bright if BARDA had taken any steps to move forward with EIDD- 2801. Dr. Kadlec made it clear that he intended to push the funding through for this contract despite Dr. Bright’s objections.
    • To that end, in late 2019, Dr. Kadlec called for a meeting with BARDA, DOD, and NIH to discuss Emory’s request for overall support of development of EIDD-2801. Dr. Bright had previously directed his staff to contact DOD and NIH to better understand the terms of their contracts with EIDD-2801, and at this group meeting convened by Dr. Kadlec, it was clearly stated that Emory had received sufficient funding through DOD and NIH to obtain the necessary data to inform further investment of government dollars. Dr. Bright again made it clear that he would not consider BARDA funding for EIDD-2801 until he had additional data from clinical trials. Although Dr. Kadlec let it be known he was very unhappy with Dr. Bright’s position on this issue, the matter was tabled temporarily, as the country began to turn its attention to the emerging threat from COVID-19.

III. With the Emergence of COVID-19, Dr. Bright pushed BARDA to innovate quickly, but within the bounds of the scientific review process.

• In late December 2019, Dr. Bright and other public health officials began taking note when a respiratory virus broke out in Wuhan, China. The CDC issued an official health advisory on January 8, 2020, and by January 11, 2020, the World Health Organization (“WHO”) had issued recommendations for countries to begin taking precautions to try to prevent the spread of COVID- 19. Given his decades of expert knowledge on pandemic influenza and emerging infectious diseases, Dr. Bright immediately understood the global reach of this virus. He recognized that lives would depend on the rapid development of effective diagnostics, treatments and vaccines and there was no time to waste. Dr. Bright acted with urgency to begin to address this pandemic but encountered resistance from HHS leadership, including Secretary Azar, who appeared intent on downplaying this catastrophic threat. According to an account in the Wall Street Journal, on January 29, 2020 – eight days after the U.S. announced its first COVID-19 case – Secretary Azar told President Trump that the coronavirus epidemic was under control and that the U.S. government had had never mounted a better interagency response to a crisis. [A. Dr. Bright encountered opposition from Administration officials as he began pressing for necessary resources to begin vaccine, drug, and diagnostic development.] On February 27, 2020, Secretary Azar testified before the U.S. House of Representatives Ways and Means Committee that “The immediate risk to the public remains low.” He added, “It will look and feel to the American people more like a severe flu season in terms of the interventions and approaches you will see.” [9 Aaron Blake, 2 Months in the Dark: the Increasingly Damning Timeline of Trump’s Coronavirus Response, WASH. POST (Apr. 21, 2020), available at https://www.washingtonpost.com/politics/2020/04/07/timeline-trumps-coronavirus-response-isincreasingly- damning/.]
• A. Dr. Bright encountered opposition from Administration officials as he began pressing for necessary resources to begin vaccine, drug, and diagnostic development.
  • • Unlike Secretary Azar, Dr. Bright and other public health officials were fully aware of the emerging threat of COVID-19 by early January 2020. It was clear to Dr. Bright almost immediately that the virus was highly contagious, spreading rapidly, and could have a high mortality rate. Dr. Bright and his staff recognized the urgent need to obtain genetic sequencing information about the virus and to acquire viruses and clinical specimens from people infected with the virus to share with laboratories and companies. While obtaining both was absolutely critical to being able to develop reliable diagnostic tools and medicines to combat the virus, Dr. Bright initially encountered indifference which then developed into hostility from HHS leadership, including Secretary Azar, as Dr. Bright and his staff raised concerns about the virus and the urgent need to act.
    • On January 10, 2020, Dr. Bright received an update from Dr. Ruben Donis, BARDA’s Deputy Director in the Influenza and Emerging Infectious Diseases Division, about the spread of the virus and he began pushing HHS leadership to obtain sequencing and virus samples from China, to no avail. In addition, Dr. Bright also began urgently pressing HHS officials to provide necessary resources to begin vaccine, drug and diagnostic development to combat COVID-19. Again, to no avail. Rather than deferring to Dr. Bright’s expertise and judgment and heeding his calls for urgent action, HHS leadership criticized him for his efforts and removed him from meetings going forward.
    • On January 12, 2020, the first novel coronavirus case was reported outside of China, in Thailand, raising levels of concern. The following day, the National Security Council set up a Policy Coordination Committee meeting for January 14, 2020, “to discuss developments associated with the novel corona virus circulating around South East Asia.” In response, Dr. Bright proposed an urgent agenda item for the meeting: “We need to get virus samples to USG colleagues ASAP. Sequences alone are insufficient for potential mcm development and assessment…. For national security, we need more.” See email from R. Bright to G. Disbrow (Jan. 13, 2020), attached hereto as Exhibit 2. Over the next several days, Dr. Bright met with ASPR and BARDA staff to discuss the outbreak and to review international reports regarding its spread. He repeatedly asked HHS Leadership to move quickly, hire more personnel, secure funding and obtain viruses to get started on medical countermeasures. His urgency was repeatedly met with seeming indifference by Dr. Kadlec who appeared to be focusing all of his attention and most of his ASPR resources on repatriating people from China and then from cruise ships with passengers infected by the Coronavirus.
    • On January 18, 2020, Dr. Bright pushed Dr. Kadlec and his ASPR policy group to coordinate senior level meetings, called Disaster Leadership Group (“DLG”) meetings, to coordinate planning activities across the government for the emerging COVID-19 outbreak. (In previous outbreaks, such as Ebola, Zika and influenza, the DLG played a central role in coordinating intergovernmental efforts to align on basic science and response activities.) Dr. Kadlec initially rejected Dr. Bright’s request to convene the DLG noting, “Don’t know if we HHS has (sic) outstanding policy issues to resolve.” See email from R. Kadlec to R. Bright (Jan. 18, 2020), attached hereto as Exhibit 3. Later that day, Dr. Kadlec responded again, suggesting that while there was value to Dr. Bright’s suggestion to convene a DLG, he was “[n]ot sure if that is a time sensitive urgency.” Id. (Emphasis added.)
    • On January 20, 2020, the WHO held an emergency call, attended by many HHS officials, during which it advised that “the outbreak is a big problem.” After the call, Dr. Bright and his team discussed the need to make HHS leadership aware of the urgent necessity for funding to combat the virus. By email dated January 20, 2020, Dr. Robert Johnson, Director of BARDA’s Division of Influenza and Emerging Infectious Diseases, asked Dr. Bright: “Is the ASPR (and hopefully through him) the S1 [Secretary Azar] aware of just how BARDA’s hands are tied due to lack of EID funding, and the precious time being lost?” (emphasis in original.) See email from R. Johnson to R. Bright (Jan. 20, 2020), attached hereto as Exhibit 4. Dr. Bright responded that despite his request, Dr. Kadlec had still not held a DLG. Later that day, the first known case of coronavirus was reported in the United States, ratcheting up the sense of alarm that an outbreak in the United States was imminent. On January 21, 2020, Brian Shuy, Dr. Kadlec’s Chief of Staff, emailed Dr. Bright and other BARDA officials requesting that they identify programmatic needs and estimate related costs. See email from B. Shuy to R. Bright (Jan. 21, 2020), attached hereto as Exhibit 5. Dr. Bright and his staff responded that virus samples and funds were urgently needed and, once again, Dr. Bright pushed Dr. Kadlec’s staff to hold a DLG. Id.
    • At the same time that Dr. Bright was pushing HHS to obtain virus samples and increase funding to BARDA, he became convinced that as COVID-19 continued its rapid spread, the Administration’s strategy of containing the virus (e.g., trying to prevent it from coming into the United States) was ill-conceived and that HHS needed to act urgently to increase supplies to be able to treat individuals who became infected when the virus began to spread in the United States. Dr. Bright was alarmed about the scarcity of critical resources and supplies, including N95 masks, swabs, and syringes, and began clashing with HHS leaders as he pressed for them to take appropriate action to address these shortages.
    • To the chagrin of HHS leaders, Dr. Bright repeatedly pushed Dr. Kadlec and the ASPR’s critical infrastructure and supply chain teams to talk to mask producers and to secure and expand the U.S. mask supply. He also continually challenged them on the urgency of actions required to get in front of what he correctly identified as critical shortage issues.
    • On January 21, 2020, Mike Bowen, co-owner and Executive Vice President of domestic surgical mask producer Prestige Ameritech, emailed Dr. Bright to inform him that the Department of Homeland Security (“DHS”) had contacted him about procuring masks. See email from M. Bowen to R. Bright (Jan. 21, 2020), attached hereto as Exhibit 6. Dr. Bright forwarded the email to Dr. Kadlec, Mr. Shuy, Dr. Laura Wolf, Director of ASPR's Division of Critical Infrastructure Protection (“CIP”), ASPR Director of External Affairs, Cicely Waters, and the SNS Deputy Director Steven Adams. Id. Dr. Bright asked Dr. Wolf to reach out to Mr. Bowen. In an email to Dr. Bright the following day, Mr. Bowen again offered to support the government in procuring masks. He explained that Prestige Ameritech had four N95 manufacturing lines that were currently not operational, but could be reactivated “in a dire situation and with government help.” He concluded the email by telling Dr. Bright, “I hope that your and my predictions about the foreign made US mask supply don’t come true.” See email from M. Bowen to R. Bright (Jan. 22, 2020), attached hereto as Exhibit 7. Dr. Bright understood that the nation would need more masks, and Mr. Bowen offered a means of production from the country’s largest mask manufacturer. He responded that afternoon to thank Mr. Bowen for his offer. He explained that he had forwarded Mr. Bowen’s information to the ASPR “critical infrastructure team” the day before, and hoped that someone from the team had already contacted Mr. Bowen. In case they had not, Dr. Bright copied Dr. Wolf and Dr. Jessica Falcon, ASPR Deputy Assistant Secretary, on the email “in hope of expediting a conversation.” Id.
    • The next day, January 23, 2020, Dr. Kadlec finally convened a DLG meeting. [10 Apparently, the pressure and visibility of now having a case in the United States and Dr. Bright’s requests to hold a meeting to align across HHS and other government partners finally sank in and Dr. Kadlec scheduled a meeting with high level leaders from numerous offices and agencies.] During the meeting, Dr. Bright emphasized BARDA’s urgent need for virus samples and a major infusion of funds for development of diagnostics, drugs and vaccines. He also expressed concerns about the shortage of N95 masks, which he correctly anticipated would cause a health care crisis among first responders and health care providers. Disturbingly, Dr. Kadlec plowed through the abbreviated meeting, addressing topics in a perfunctory manner and paying short shrift to the concerns that Dr. Bright raised.
    • Also on January 23, 2020, Dr. Bright attended a meeting with HHS senior leadership across all agencies to brief Secretary Azar on COVID-19. Anticipating the urgency and magnitude of the threat and knowing the lead times needed to develop new drugs, diagnostics, and vaccines, Dr. Bright pressed for urgent access to funding, personnel, and clinical specimens, including viruses, which he emphasized were all critically necessary to begin development of lifesaving medicines needed in the likely event that the virus spread outside of Southeast Asia. Secretary Azar and Dr. Kadlec responded with surprise at Dr. Bright’s dire predictions and urgency, and asserted that the United States would be able to contain the virus and keep it out of the United States. Secretary Azar further indicated that the CDC would look at the issue of travel bans to keep the virus contained. Dr. Bright responded that virus “might already be here. We just don’t have the tests to know one way or the other.” Dr. Bright’s comments were met with skepticism and were clearly not welcome. Nonetheless, he continued to press his point that the situation was dire and that money was urgently needed to develop diagnostics and drugs to combat the virus when it eventually spread to the United States. Secretary Azar then questioned Dr. Bright about BARDA’s funding to combat the virus, to which Dr. Bright replied that BARDA had no funds available for emerging infectious diseases to meet the challenges of this pandemic, and that BARDA would be forced to re-direct funds from existing projects until new funding was made available. Secretary Azar also asked the representative from the Assistant Secretary for Financial Resources (“ASFR”) about availability of funding for the response. It was evident from Secretary Azar’s reaction that this topic had not yet been raised at senior HHS levels.
    • Consistent with the attitude of Secretary Azar and Dr. Kadlec, HHS’s public statements at the time likewise reflected no real sense of urgency. To the contrary, HHS publicly represented not only that COVID-19 was not an imminent threat, but also that HHS already had all the masks it would need. On January 23, 2020, an HHS spokesperson stated that “CDC believes that the immediate risk to the U.S. public is low at this time.” See Gretchen Michael, “Media Key Points” (Jan. 23, 2020), attached hereto as Exhibit 8. HHS also stated that the SNS “holds millions of face masks as well as N95 respirators that could be used if needed in responding to a public health emergency when local supplies are exhausted and aren’t available from commercial suppliers.” [11 See Jennifer A. Kingson, Coronavirus Fears Spark Run on Surgical Face Masks in U.S., AXIOS (Jan. 27, 2020), available at https://www.axios.com/coronavirus-surgical-face-masks-america-2cdae7d0- edf4-4d29-b24e-b10f16cbcd84.html.]   As a result of the critical concerns raised by Dr. Bright in the January 23, 2020, meeting with Secretary Azar, HHS leadership excluded him from the next COVID-19 meeting, even though the agenda listed Dr. Bright as a participant. Mr. Shuy later told Dr. Bright that his request for urgent funding at the meeting on January 23th set off “quite a shit storm” after the meeting. Mr. Shuy further relayed to Dr. Bright he had offended HHS leadership by pushing for urgent funding, he had offended HHS leadership. According to Mr. Shuy, HHS leadership believed that BARDA already had a sizable budget, albeit nothing specifically for COVID-19, and that he should not have asked for additional resources to address the virus.
    • On January 23, 24 and 25, 2020, Mr. Bowen from Prestige Ameritech repeatedly emailed Dr. Bright and Dr. Wolf to sound the alarm yet again about the mask shortages. HHS failed to act yet again to address this impending emergency.
    • On January 25, Mr. Bowen wrote Dr. Bright and Dr. Wolf that his company was “getting lots of requests from China and Hong Kong.” He then explained that nearly 50% of masks in the United States are imported from Chinese manufacturers, and “[i]f the supply stops, US hospital will run out of masks. No way to prevent it.” See email from M. Bowen to R. Bright (Jan. 25, 2020), attached hereto as Exhibit 9. Dr. Bright forwarded Mr. Bowen’s email to the “CIP Supply Chain,” Dr. Wolf, Dr. Falco, and Mr. Adams, with a note that “[t]he mask situation seems to be of concern and we have been receiving warnings for over a week.” Id. Dr. Bright told the team that it was “[i]mportant to keep this at the top of the heap of various issues.” Id. As other countries were vying for the Unites States mask supply, Dr. Bright continued to put pressure on HHS leadership to take action, to no avail.
    • It became increasingly clear to Dr. Bright that HHS leadership was doing nothing to prepare for the imminent mask shortage, which Dr. Bright correctly recognized would hinder the ability of medical care providers and first responders to respond to this impending medical crisis. Accordingly, on that same day, January 25, 2020, Dr. Bright emailed Dr. Johnson and Dr. Disbrow about considering providing financial support to Prestige Ameritech to reopen its defunct factories. Dr. Johnson responded that he thought masks were within SNS’s purview and budget. Nonetheless, Dr. Bright was skeptical that the SNS would move with the necessary urgency. That evening, Dr. Bright alerted Dr. Kadlec of the problem and encouraged him to accelerate a solution: “Hearing face mask supply is also getting very low as China and HK trying to procure. I’ve alerted cip on this throughout week. May need to consider options here also before things are gone.” See email from R. Bright to B. Kadlec (Jan. 25, 2020), attached hereto as Exhibit 10.
    • The next morning, Mr. Bowen emailed Dr. Bright that the “U.S. mask supply is at imminent risk.” See email from M. Bowen to R. Bright (Jan. 26, 2020), attached hereto as Exhibit 11. Dr. Bright forwarded this dire warning to Dr. Kadlec, Dr. Wolf, Dr. Falcon, Dr. Disbrow, Dr. Johnson, Dr. Adams, and others, so they could see the basis for his alarm and insistence that action be taken at once. He wrote, “We have been watching and receiving warnings on this for over a week.” He then encouraged CIP and SNS to “consider an action plan.” Id. Dr. Bright wrote Mr. Bowen that stating: “I know that our critical infrastructure protection team has been in contact with you.” The next morning, Mr. Bowen responded, “I’ve spoken with Laura. Rick, I think we’re in deep shit. The world.” Id.
    • Alarmed by HHS’s inaction, on January 27, 2020, Dr. Bright emailed Dr. Disbrow to complain that Prestige Ameritech’s requests for support to accelerate mask manufacturing “seem[] to be falling on deaf ears.” Understanding that HHS was not taking the necessary steps to prevent a mask shortage, Dr. Bright asked Dr. Disbrow whether BARDA should “put in a budget request to assist.” [12 In BARDA’s initial budget formulation documents, a line item was included to expand domestic mask manufacturing lines. In the various internal discussions with ASPR, ASFR and BARDA, mostly lead by Mr. Shuy, BARDA was told to remove the budget request for mask production, that it purportedly was already covered in the ASPR and SNS budget line.] Id. Later that day, Dr. Falcon emailed Dr. Bright to assure him that her office was “having discussions” about the mask concern. See email from J. Falcon to R. Bright (Jan. 27, 2020), attached hereto as Exhibit 12.
    • Also on January 27, 2020, Dr. Bright received an email from Dr. Larry Kerr, Director of Pandemics and Emerging Threats in HHS Office of Global Affairs, expressing an urgent need to talk about the CDC’s failure to take appropriate actions to respond to the pandemic. See email from L. Kerr to R. Bright (Jan. 27, 2020), attached hereto as Exhibit 13. He stated: “CDC just told the Secretary for his call with Minister Ma that [virus] samples from China are not needed and to de-prioritize it on the upcoming call. We fought back and I think he is still going to raise it but we need BARDA, NIH and FDA to speak up. The USG needs requirement is clear but CDC leadership is not saying that.” Id. Dr. Bright replied that “[w]e cannot emphasize enough the critical need to access virus to initiate MCM development.” See email from R. Bright to L. Kerr (Jan. 27, 2020), attached hereto as Exhibit 14. Dr. Kerr responded that, as of that day, no one had officially asked China for samples. He further noted that Secretary Azar had had a call with China’s Health Minister that morning but did not raise the need for virus samples. [13 According to Dr. Kerr, in the pre-brief before Secretary Azar’s call with the Chinese Health Minister, it was emphatically expressed that BARDA, NIH, and FDA all disagreed with CDC’s position and emphasized to Secretary Azar that there was an urgent need to secure a panel of viruses from China for MCM development.] Dr. Bright expressed disbelief at Secretary Azar’s failure to request virus samples, to which Dr. Kerr replied that “Bob (Kadlec) was on the call but didn’t speak up.” Id.
    • That same morning [of January 27 2020], Dr. Bright participated in a COVID-19 meeting chaired by HHS Deputy Secretary Eric Hargan in Dr. Azar’s absence. During the meeting, Dr. Bright expressed frustration with the slow pace of accessing virus samples and/or clinical specimens from China, which he explained were critical to begin development of vaccines, diagnostics, and medicines. Dr. Bright asked pointedly why the CDC, which was securing viruses from other countries, was delaying providing them to BARDA or to companies to allow for MCM development. Dr. Nancy Messonnier, Director of the National Center for Immunization and Respiratory Diseases (“NCIRD”) at the CDC, who was participating by telephone, responded that Dr. Bright should know better than to make that request because he was well aware that the CDC had agreements with other countries that restricted it from sharing virus specimens with other entities, even within the government. Dr. Bright asked Dr. Messonnier to explain why these restrictions were in place and why BARDA could not use the material to get started on MCM development critical to save American lives. Dr. Messonnier became angry and chastised Dr. Bright, insisting that he “take the topic offline.” [14 Over the next few days, Dr. Bright and his team, at Dr. Bright’s direction, feverishly emailed health officials and laboratories in Australia, Thailand, the United Kingdom and France to try to obtain samples because the CDC had refused to provide information or virus samples to them. It was not even clear to Dr. Bright which virus samples, from the United States or other countries, the CDC actually had because the CDC refused to make this information available to other governmental agencies due its “contractual obligations” to the provider of the samples. Dr. Bright was alarmed by CDC’s insistence that it adhere to contractual obligations that clearly impeded the government’s ability to develop medical counter-measures to save lives.]  Deputy Secretary Hargan, who was observing the conversation play out, gave Dr. Bright a hand signal to stop talking. It was clear to Dr. Bright that his inquiries had created tension.
    • The following day, Dr. Bright sent a note to Dr. Kerr to ask if the daily COVID-19 meetings with Secretary Azar were still occurring. Dr. Kerr confirmed that they were, but explained that due to the “commotion” in the meeting the day before, Judy Stecker, a high-level aide to Secretary Azar, decided that there were too many attendees and cut the list. Later that day, Dr. Bright sent an email to Dr. Kerr noting that he had heard that BARDA had been removed from briefings to Secretary Azar and asked if he had any insights. See email from R. Bright to L. Kerr (Jan. 28, 2020), attached hereto as Exhibit 15. Dr. Kerr responded that the decision to eliminate BARDA was made by Brian Harrison, Secretary Azar’s Chief of Staff, and Ms. Stecker, who decided that only Dr. Kadlec and his chief of staff, Mr. Shuy, who is not a scientist, would be permitted to attend and would present for BARDA. Id. It was obvious that Dr. Bright’s persistent demands for urgent action to respond to the pandemic had caused a “shit storm” and a “commotion” and were unwelcome in the office of the HHS Secretary. As a result, HHS leadership excluded Dr. Bright and BARDA from these recurring meetings and from the critical discussions about addressing the COVID-19 pandemic.
    • On January 29, 2020, Dr. Falcon sent another update to Dr. Kadlec, Dr. Bright, Mr. Shuy, and others regarding “Identified Medical Supply Chain Focus Areas,” which included N95 and surgical masks, and “Concerns/Additional Analysis,” which included the predominantly foreign production of masks. See email from J. Falcon to B. Shuy (Jan. 29, 2020), attached hereto as Exhibit 16. Dr. Falcon’s email did not list any action items, and despite weeks of warnings from Dr. Bright, industry leaders, and international media, her office was still not yet taking any action to procure masks. Two days later, Mr. Bowen of Prestige Ameritech sent yet another email to Dr. Bright and Dr. Wolf, once again issuing a dire warning about the imminent mask shortage. Id. Among other things, he advised “[t]his week, we sent 1,000,000 masks to China and Hong Kong. He continued, “[i]n all my years of predicting the US mask supply would one day collapse, I never pictured myself selling masks to China…. I have it from two reliable sources that China has begun telling Chinese mask makers not to let masks leave China.” He concluded, “I think China will cut off masks to the USA. If so, US hospitals are going to have a very rough time, as up to half of the supply is made in China. A horrible situation will become unbearable.” See email from L. Wolf to R. Bright (Jan. 29, 2020), attached hereto as Exhibit 17. (emphasis added). Dr. Wolf followed up with Dr. Bright to let him know that CIP and CDC were working with N95 manufacturers and distributors. She told Dr. Bright that “[t]here is cause for concern, but not panic.” Id.
    • On February 3, 2020, Mr. Bowen sent yet another dire warning about the mask supply shortage and urged Drs. Bright and Wolf to speak to a New York Times reporter whom Bowen had contacted about this growing threat. He urged them to speak to the media “to make the president aware of this little known national security risk. If we let this opportunity go by, the US mask supply will forever remain under foreign control. Trump reads the news.” See email from M. Bowen to R. Bright (Feb. 3, 2020), attached hereto as Exhibit 18. Dr. Bright did not speak with the reporter, but instead followed the chain of command and referred the matter to HHS’s communications team. By February 4, 2020, the media was reporting an impending global mask shortage. [15 Maryn McKenna, Amid Coronavirus Fears, a Mask Shortage Could Spread Globally, WIRED (Feb. 4, 2020), available at https://www.wired.com/story/amid-coronavirus-fears-a-mask-shortage-couldspread- globally/ (quoting Mr. Bowen).] Unfortunately, the public exposure of this aspect of the impending health crisis did not cause HHS leadership to act. That week, noting that no other office was taking appropriate action, Dr. Bright directed BARDA to revise its budget to include expenses to ramp up domestic mask production. However, in the following weeks of budget negotiation between BARDA, ASPR and ASFR, it was determined that the budget for masks would be covered under the ASPR SNS budget and removed from the BARDA budget request.
    • During late January/early February 2020, Dr. Bright also launched a comprehensive review of existing drugs that had been developed for MERS, SARS, Ebola and other viruses to urgently determine if there might already be a drug available or in late stage development that could work against the novel coronavirus. Dr. Bright had BARDA create a landscape chart that showed all possible vaccine, therapeutic and diagnostic candidates that might be efficacious in the treatment of the novel coronavirus. In addition, BARDA had made significant investments in various drug and vaccine platform technologies – common backbones and production systems used to make vaccines and treatments for other viral threats that could be leveraged to move much faster to develop a treatment or vaccine for the novel coronavirus. Dr. Bright had his team chart and prioritize these platforms for rapid assessment of their potential for use in the outbreak. In addition, Dr. Bright directed his team to review all existing contracts and agreements to assess which agreements could be quickly refocused to address the novel coronavirus. This strategy had been put in place at BARDA over the last five years to respond quickly to emerging infectious diseases. Under Dr. Bright’s direction, BARDA was executing its long-standing strategic plan for rapid response to an emerging virus.
    • In conducting this assessment, Dr. Bright became concerned about the limited supply of Remdesivir, a broad-spectrum antiviral medication developed by Gilead Sciences (“Gilead”) that appeared, based on limited data coming from China and some laboratory-based testing, to lower the number of days it took patients to recover from COVID-19. After reviewing available scientific and medical literature, Dr. Bright and HHS and global clinicians determined that Remdesivir had the highest probability of an existing drug for being efficacious for treating people with COVID-19. He further determined that Gilead’s supply of the drug was low – it had only a few thousand doses of the drug on hand and the timeline to manufacture more was lengthy. He repeatedly advised Dr. Kadlec and other HHS officials of the urgent need to acquire the existing doses and to secure future doses as they were produced. He also strongly recommended that HHS work with Gilead to “on-shore” all steps of the Remdesivir supply chain to ensure an uninterrupted supply in the United States. Once again, Dr. Bright’s urgent requests for concrete measures such as these only escalated tensions with HHS leadership, which apparently wished to downplay the risk of the virus and therefore intended to marginalize him and exclude him from key meetings as he continued to sound the alarm.
    • On February 7, 2020, the DLG met and, at Dr. Bright’s urging, focused on the topic of masks and respirators. Dr. Bright and Dr. Anita Patel from the CDC reminded DLG members of previous FRMM reviews, models and publications which cited a need for up to 3.5 billion N95 masks to respond to a pandemic. Dr. Bright reiterated that the United States had a significant shortage and raised concerns that the exportation of masks further depleted an already inadequate supply. He insisted that the federal government urgently needed to place orders to ramp up production of N95 masks in order to ensure that health care workers and first responders were adequately protected. This was crucial to ensure their own safety and also to prevent the spread of COVID-19 in hospitals and other medical settings. ASPR supply chain leads pushed back, insisting that there was no indication of a supply chain shortage or of issues with masks, and therefore there was no need to take immediate action. Dr. Bright responded that the country was already seeing shortages in drug stores and online and it was clear that there was going to be a dangerous shortage of masks as the virus continued to spread. Dr. Wolf and Dr. Falcon responded that the plan was to monitor for any supply chain issues and, if needed, ask the CDC to update its guidelines to tell people who “don't need” masks to not buy them. Dr. Bright responded, “I can't believe that you can sit there and say that with a straight face. Do you really believe that changing a CDC guideline to tell people not to wear masks would reduce the panic people would feel once this virus spreads?” He again emphasized the need to contact mask producers to place orders immediately.
    • Fortunately, White House Trade Advisor Peter Navarro shared Dr. Bright’s sense of urgency, recognized his expertise, and was prepared to help. Mr. Bowen, who continued to raise concerns about the dire consequences of the mask shortage in the United States, connected Mr. Navarro with Dr. Bright. On February 5, 2020, Mr. Bowen sent Dr. Bright an email marked “High Importance,” with the subject line: “Prepare for a call from the White House.” He stated: “I’m pretty sure that my mask supply message will be heard by President Trump this week. I’m getting a ton of press and saying that you’re the guy who knows that I’m telling the truth. Thanks to a Trump insider reading yesterday’s Wired.com article the ball is screaming toward your court. I’m handing you the power to fix the US mask supply. Please don’t let American (sic) down.” See email from M. Bowen to R. Bright (Feb. 5, 2020), attached hereto as Exhibit 19. Mr. Bowen continued: “I’m also telling people that you [and the former director of BARDA] are exemplary public servants. I know that you’re doing what’s in your power… Please ask your associates to convey the gravity of this national security issue to the White House. I’m pretty sure you’ll get the chance.” Id. Dr. Bright again followed the chain of command and made the ASPR office was aware of Mr. Bowen’s entreaty that day by email. The following day, the Wall Street Journal ran an article about the mask shortage, once again sounding the alarm. [16 See Austen Hufford, Coronavirus Outbreak Strains Global Medical-Mask Market, Wall St. J. (Feb. 6, 2020), available at https://www.wsj.com/articles/coronavirus-outbreak-strains-global-medicalmask- market-11580985003.] And once again, HHS Leadership failed to act. 
    • For that reason, on February 7, 2020, Dr. Bright was greatly surprised and relieved to receive a telephone call from Mr. Navarro’s policy assistant, Joanna Miller, who was with Mr. Navarro in the White House Situation Room. Ms. Miller asked Dr. Bright to meet with Mr. Navarro and members of his staff the following day at the White House to brief them about coronavirus response activities. Dr. Bright told Ms. Miller that he was eager to meet with Mr. Navarro but required the approval of HHS leadership to attend the meeting. He then immediately contacted Dr. Kadlec to obtain authorization to attend. Dr. Kadlec informed Dr. Bright that he (Kadlec) needed to discuss the request with Secretary Azar. As the meeting time approached, Dr. Kadlec had still not responded to Dr. Bright’s request to attend the meeting with Mr. Navarro. When Dr. Bright notified Mr. Navarro that he had not obtained clearance to attend the meeting, Mr. Navarro called both Dr. Kadlec and Brian Harrison, Secretary Azar’s Chief of Staff, directly. A few minutes later Dr. Kadlec emailed Dr. Bright, “you (sic) cleared to attend. Thank you for advising.” See email from R. Kadlec to R. Bright (Feb. 8, 2020), attached hereto as Exhibit 20. Even though Dr. Kadlec authorized Dr. Bright to attend the meeting, he was extremely uncomfortable that Dr. Bright had agreed to meet with Mr. Navarro. Dr. Bright later learned that Mr. Shuy had sent Ms. Miller two emails trying to dissuade Mr. Navarro from meeting with Dr. Bright. After Dr. Bright and Mr. Navarro met, Dr. Kadlec and other members of HHS leadership made disparaging remarks about Dr. Bright’s interactions with Mr. Navarro and the White House.
    • At 2:00 p.m. on Saturday, February 8, 2020, Dr. Bright met with Mr. Navarro at the White House. Dr. Bright found Mr. Navarro to be deeply engaged in the issues confronting the United States in responding to the rapidly approaching pandemic. Mr. Navarro clearly shared Dr. Bright’s concerns about the potential devastation the United States would face from the coronavirus and asked Dr. Bright to identify the supply chain and medical countermeasures most critical to address at that time in order to save lives. Dr. Bright emphasized the need to secure N95 masks and to ramp up mask production. He also informed Mr. Navarro about other actions that were urgently needed to develop diagnostic tools, drugs, and ultimately a vaccine, to combat the virus. In the short run, Dr. Bright urged Mr. Navarro to take immediate action to increase the mask supply, amass Remdesivir, and fund and initiate a “Manhattan Project” for vaccine development. Unlike Secretary Azar, Dr. Kadlec and other members of HHS leadership who dismissed Dr. Bright’s assessments and urgent requests and excluded Dr. Bright from key meetings, Mr. Navarro asked good questions and was prepared to take prompt action to address this impending health crisis. Mr. Navarro clearly recognized that Dr. Bright was unable to get any traction with HHS and was, to Dr. Bright’s great relief, prepared to act.
    • Indeed, the following day, Mr. Navarro invited Dr. Bright to return to the White House to assist him in preparing a memorandum to the White House Coronavirus Task Force urging it to direct HHS leadership to take three critical steps. In this memorandum, which Mr. Navarro sent through President Trump’s Chief of Staff, Mick Mulvaney, and President Trump’s National Security Advisor, Robert O’Brien, he identified three actions to be undertaken “IMMEDIATELY.” See “Memorandum to the Task Force,” (Feb. 9, 2020), attached hereto as Exhibit 21. They were: 1) immediately halt the export of N95 masks and ramp up U.S. production of masks; 2) secure all existing doses of Remdesivir and all bulk materials to make more and enter into a contract with Gilead to purchase all additional doses as they are produced; and 3) immediately fund and initiate a "Manhattan Project" for vaccine development. In explaining the need for a Manhattan Project for vaccine development, Mr. Navarro stated in the memo:
      • • There is currently no vaccine to protect against coronavirus. If we start this week to fast track vaccine development with appropriate funding, we can likely have a vaccine to clinical trials within 7 months and a workable vaccine by October or November, with a production capacity of 150 million doses by the end of the year IF we act NOW. We don’t yet know what type of vaccine would be safe and effective. Therefore, it is critical the USG invest in multiple shots on goal to ensure that at least one vaccine is realized. Efforts should be prioritized to focus on USbased vaccine companies with extensive experience with being licensed by the FDA or with significant human safety data.
    • Mr. Navarro ended the memorandum stressing the importance of leaving the next task force meeting with a firm decision to immediately advance all three recommendations and warned that “[i]naction at this point risks losing our Remdesivir drug supply, our N-95 production capabilities, and any head start we may have on a vaccine for next year.” Id. [17 Dr. Kadlec criticized Dr. Bright for his insistence that the U.S. start working on vaccines at the outset of the pandemic, stating that the focus should be on drugs because vaccines would take too long to develop. It took Secretary Azar until April 10, 2020, to focus on the need to prioritize vaccines and to come up with a Manhattan Project for vaccine development. Indeed, it was not until the period between April 13 to April 17, 2020, when Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research, presented his “Project Warp Speed” project to Secretary Azar that he (Azar) embraced such an approach. By the time Secretary Azar and others in HHS Leadership focused their attention on vaccine development, BARDA, under Dr. Bright’s leadership, already had 40 contracts in place with companies to rapidly develop medical countermeasures for COVID-19, three of those were for vaccines with more contracts were in negotiation.]
    • The following day, Monday, February 10, the National Security Council Policy Coordination Committee met and directed Dr. Kadlec and HHS leadership to implement Mr. Navarro’s recommendations. This push by the White House for HHS to act more swiftly created tension between Dr. Bright and HHS political leadership because they knew that by meeting with Mr. Navarro, Dr. Bright had clearly played a key role in getting the White House Task Force to issue these directives. Dr. Kadlec in particular was uneasy about Dr. Bright’s time with Mr. Navarro, and he and other employees in Secretary Azar’s office kept tabs on their communications. That same day, Dr. Bright sent Dr. Kadlec a detailed email briefing him about the areas he had discussed with Mr. Navarro. See email from R. Bright to R. Kadlec (Feb. 10, 2020), attached hereto as Exhibit 22. While Dr. Kadlec blandly responded “thanks Rick” to that email, he sent another email to Mr. Harrison, Ms. Stecker, and Mr. Mango, copying Dr. Bright and Mr. Shuy, with a subject line “Weekend at Peter’s” that was a clear jab at Dr. Bright. In it, he suggested that “it may be worthwhile to get a back brief from Rick Bright on his time with Navarro.” See email from B. Kadlec to B. Harrison (Feb. 10, 2020), attached hereto as Exhibit 23. There was no follow up on this suggestion and no one at HHS asked Dr. Bright to provide them with a debriefing.
    • While Dr. Kadlec remained uncomfortable with Dr. Bright’s access to the White House, he was left with no choice but to implement actions that mirrored those set out in Mr. Navarro’s memorandum. At an ASPR Senior Leadership meeting on February 10, 2020, Dr. Kadlec announced an urgent directive to his staff that included, as its top three priorities: (1) stopping exports of masks and preparing for an increased demand for N95s; (2) buying all existing Remdesivir; and (3) managing vaccine candidates like a “Manhattan Project.” See email from L. Lambert to R. Bright (Feb. 12, 2020), attached hereto as Exhibit 24. Because of Dr. Bright’s meeting with Mr. Navarro, HHS had for the first time committed to taking certain actions to protect the country’s supply of masks, among other things.
    • Despite Dr. Bright’s best efforts, to connect mask producers to the ASPR supply chain leads so they could hear first-hand from manufacturers about the growing shortage, this urgent issue had not been effectively addressed. Accordingly, Dr. Bright continued to offer dire warnings and forward reports of mask shortages to the ASPR’s SNS and Critical Infrastructure teams. But while more discussion was occurring, little action was taking place to address this significant risk. Indeed, on February 14, 2020, Dr. Kadlec and Mr. Shuy were asked to brief Mr. Navarro on medical supply chain issues and asked the ASPR supply chain leadership to prepare slides for the meeting. Shockingly, the conclusion was that “there are no known immediate problems with supply chains” even though there was an acknowledgement that the United States could require up to 6 billion respirators in a pandemic, and that it was “[u]nlikely that the US will have enough disposable N95 respirators to meet response needs under current infection control recommendations.” See COVID-19 (2019-nCoV): Medical Supply Chain (Feb. 14, 2020) (slide deck), attached hereto as Exhibit 25, at pages 3 and 4. Later in the report, ASPR identified other critical products of concern, including face shields, needles, syringes, and antimicrobials, and identified as important issues of concern a shortage of gloves and gowns. Id at pp. 12-13. Thus, even as HHS leadership began to acknowledge the imminent shortages in critical medical supplies, they failed to recognize the magnitude of the problem, and they failed to take the necessary urgent action.
    • Later in the day on February 14, Dr. Bright returned to the White House at Mr. Navarro’s request to assist him in drafting several more urgent memos in preparation for the Task Force that were necessary, in Mr. Navarro’s words, to “get shit done” and “save lives.” Dr. Bright briefed Mr. Navarro about the meeting referenced above and its conclusions, and like Dr. Bright, Mr. Navarro was extremely concerned about HHS’s laxity in addressing the pandemic. He requested Dr. Bright’s assistance in drafting memoranda to the White House Task Force about production of N95 masks, respirators, vaccines, therapeutics, diagnostics and ancillary supplies such as needles and syringes that were critical to administer vaccine. In the course of this and other meetings, Dr. Bright briefed Mr. Navarro about the urgent need to develop rapid, hand-held diagnostic and serology tests and potential shortages of materials necessary to administer COVID-19 tests, such as swabs and extraction buffers. He made clear that the lack of masks and protective equipment put health care workers at serious risk and that without adequate masks and Personal Protective Equipment (“PPE”), they would be extremely vulnerable to infection. He also discussed with Mr. Navarro his growing alarm about the shortage of syringes, needles and vials necessary to administer vaccines if and when one became available.
    • At the conclusion of the February 14th meeting, Mr. Navarro drafted five separate memoranda to the White House Task Force, urging: the production of N95 masks; the creation of a Manhattan Project for the development of oral antiviral drugs; the mass production of manufacture of needles and syringes; the development of handheld diagnostic and serology tests; and the development of monoclonal antibodies for potential prophylactic use to protect healthcare workers and other critical workers until a vaccine became available.
    • Mr. Navarro sent three memoranda to the COVID-19 Task Force, through Mr. Mulvaney and Mr. O’Brien, urging immediate action to increase production of Remdesivir, increase the N95 face mask supply, and ramp up production of needles and syringes necessary to deliver a vaccine. See “Memo to Covid-19 Task Force: Ramp Up Production of Ancillary Supplies,” (Feb. 14, 2020), attached hereto as Exhibit 26; “Memo to Covid-19 Task Force: Expand Remdesivir Production to Include a US-Based Production Facility,” (Feb. 14, 2020), attached hereto as Exhibit 27; “Memo to Covid-19 Task Force: Status of N-95 Face Mask Supply,” (Feb. 14, 2020), attached hereto as Exhibit 28. With respect to the ancillary supplies issue, Mr. Navarro stated:
      • • We face an urgent need to administer large quantities of vaccine once produced. An estimated 850M needles and syringes are required to deliver vaccine. Our current inventory of these supplies is limited and, under current capabilities, it would take up to two years to produce this amount of specialized safety needles. We may find ourselves in a situation where we have enough vaccine but no way to deliver all of it.
    • Id. (Emphasis added.) Mr. Navarro made the following recommendations, all of which Dr. Bright had suggested:
      • • Recommendations
          • •  Direct OSHA and CDC to take steps to liberalize the current policies to allow for the use of non-specialized needles to administer vaccines. Current delivery is with specialized needles with safety caps that have limited production capacity. This one change would significantly increase available inventory.
            •  Provide HHS Strategic National Stockpile with immediate funding to place orders to ramp up US production to full capacity for needles and syringes needed to deliver a vaccine. We need to immediately determine budget needs and allocate accordingly.
            •  Direct HHS BARDA to initiate a program to identify all alternate vaccine delivery methods and ramp up production. Other delivery possibilities include jet injectors and similar devices, some of which are already approved to deliver influenza vaccines.
    • Id.
    • On February 15, 2020, the “Shortages Team” within the FDA Center for Devices and Radiological Health, Office of Product Evaluation and Quality, emailed Prestige Ameritech President Dan Reese, requesting that he complete a five-page form about his company’s ability to manufacture PPE for the “national emergency response” to COVID-19. Mr. Reese forwarded the request to Mr. Bowen, who responded to the FDA by criticizing the government for being so slow to act. Mr. Bowen was angry and frustrated that Prestige Ameritech had repeatedly warned the government about the imminent mask shortage, invited them to discuss with him ways to address the issue, and had received no response, other than a form email five weeks later.
    • On February 16, 2020, Mr. Bowen emailed FDA leadership, and copied Dr. Bright, stating: “BARDA/HHS is the only government agency that understood that America’s fragile, foreign controlled mask and respirator supply was a national security problem. If they’d had the authority or if the VA and DOD had listened to them, BARDA’s leaders, Rick Bright and Robinson, would have secured the mask supply.” See email from M. Bowen to FDA (Feb. 16, 2020), attached hereto as Exhibit 29.
    • In late February 2020, as the number of confirmed positive COVID-19 cases in the United States approached 60, HHS leadership acknowledged that they were not prepared for a pandemic. When Secretary Azar testified before the Senate Appropriations Committee on February 25, 2020, he revealed that the SNS holds 30 million N95 respirators, yet “Dr. Kadlec mentioned to the Senate this morning needing approximately 300 million for health care workers.” [18 See Jenni Fink, America has 30 Million Masks, Needs 300 Million for Health Care Workers Fighting Coronavirus, HHS Secretary Says, NEWSWEEK (Feb. 25, 2020), available at https://www.newsweek.com/alex-azar-coronavirus-masks-30-million-have-need-30-million-fightamerica- senate-committee-1489058.] As calculated by previous FRMM reviews, the actual estimated number of disposable N95 respirators to protect healthcare workers in a pandemic response approached 3.5 billion – over ten times the number Dr. Kadlec represented was necessary, and over 100 times the number available in the SNS. The following day, five weeks after Dr. Bright first urged immediate action to prevent a mask shortage, ASPR finally put out a pre-solicitation to collect information from mask producers to get information on where they might be able to buy N95 respirators and face masks. Three days later, the extent to which HHS officials underestimated the mask shortage became clear when the Surgeon General encouraged the public to stop buying masks, warning that a mask shortage could take important resources from health care professionals. [19 See Maria Cramer, Surgeon General Urges the Public to Stop Buying Face Masks, NY TIMES (Feb. 29, 2020), available at https://www.nytimes.com/2020/02/29/health/coronavirus-n95-facemasks. html.] Following the ASPR SNS presolicitation notice to procure N95 masks, ASPR released a RFP to procure N95 respirators that closed on March 12, nearly two months after Dr. Bright began pushing for awareness and urgent action.
    • HHS leadership’s refusal to heed Dr. Bright’s warnings about the shortage of needles and syringes to administer a potential vaccine was yet another serious point of tension between Dr. Bright and HHS leadership, including Dr. Kadlec. In January 2020, BARDA started forming partnerships to accelerate the development of vaccines to prevent COVID-19 illness and death. BARDA estimated that between 650 million and 850 million needles and syringes would be needed to administer a vaccine for the United States alone. Dr. Bright’s team further estimated that it could take up to two years to be able to produce enough of these supplies to deliver the vaccine. The SNS currently contains approximately 15 million needles and syringes, a mere 2% of the required amount. From late January through March 2020, Dr. Bright pushed the ASPR and Federal Emergency Management Agency (“FEMA”) supply chain groups to take swift and urgent action to place orders to secure limited supplies in the U.S., ramp up production, and begin stockpiling needles and syringes immediately.
    • During an HHS leadership call on March 13, 2020, Dr. Bright raised the issue with Dr. Kadlec directly, emphasizing the urgent need to halt the export of needles and syringes, place orders to buy, and ramp up production. Dr. Kadlec responded in a frustrated and dismissive manner, telling Dr. Bright that they should wait to act until they had something to inject. Dr. Bright pushed back, arguing that it was imperative to order the needles and syringes immediately to ensure that the United States would have them when a vaccine became available. As noted above, Dr. Bright raised concerns about this issue with Mr. Navarro during their meeting on February 14, 2020 and again in March. In turn, Mr. Navarro raised these issues to the White House Task Force. Dr. Bright and his team reiterated the dire consequences of these shortages and the need to take urgent action to begin stockpiling this life-saving equipment. Instead of heeding his recommendations, ASPR and FEMA staff sent Dr. Bright numerous emails indicating that there was a lack of clarity about which agency – HHS or FEMA – should buy the needles. In passing the buck back and forth, no group had yet placed orders for these critical supplies. [20 In addition to identifying the need to purchase basic but critical supplies to administer the vaccine, Dr. Bright also raised concerns about a global shortage of glass vials that are required for vaccine production. According to major glass producers, all major pharmaceutical tubing suppliers are sold out of borosilicate tubing. It could take up to two years to produce enough vials for U.S. vaccine needs, while some therapeutics will also require vials. Dr. Bright advised leadership to devise an immediate strategy to address this critical shortage, to no avail.]
    • Dr. Bright revisited the issue with HHS Leadership on March 12, 2020. He sent an email to Dr. Wolf, Mr. Adams, and SNS Director Kevin Cooper, advising them of the following:
      • • [W]e are hearing rumblings about the US inventory of needles and syringes (critical ancillary supplies for vaccine and some therapeutics administration) are heading to other countries. There is a limited inventory in the supply chain, it could take 2+ years to make enough to satisfy the US vaccine needs for a pandemic. We need to hold on to all that we have and look at surging supplies now from producers.
    • See email from R. Bright to L. Wolf (Mar. 12, 2020), attached hereto as Exhibit 30. He ended the email by urging them to attend to this crucial supply issue “so we are not chasing things down when we need them later and they are all procured by other countries.” Id. Mr. Adams responded that he completely agreed with Dr. Bright’s concerns “but the challenge may be finding the funding.” Id. Dr. Bright then raised the issue directly with Dr. Kadlec, who again responded in a dismissive manner. Dr. Bright did not relent, however, and argued persistently for the need to order needles and syringes to have them available. Dr. Kadlec suggested that the needles and syringes could possibly be ordered in small tranches per month, instead of placing one large order. To date, HHS has still not placed an order for these critical supplies. Lack of leadership and action by the ASPR SNS organization has placed the health and safety of all Americans at risk of not being protected from the deadly coronavirus even when a vaccine becomes available.
    • Between February and March, Dr. Bright met with Mr. Navarro six or seven more times. During each meeting, he briefed Mr. Navarro about drug supply issues and gaps in domestic drug manufacturing capacity, and his ongoing concerns about the shortages in masks, PPE for healthcare workers and first responders, needles and syringes, rapid handheld diagnostics, serology tests, vaccines, oral antiviral drugs and monoclonal antibodies for potential prophylactic use. After many of these meetings, Mr. Navarro sent memoranda to the White House Chief of Staff and Task Force members urging immediate action and implicitly criticizing HHS leadership for its failure to act. While Dr. Bright believed that the criticisms were warranted, he continued to try to handle these issues up his chain of command. Unfortunately, HHS’s leadership acted with increased hostility towards Dr. Bright and made disparaging comments about the pressure they were receiving from “Rick’s friend” in the White House. Ultimately, even the White House started referring to Dr. Kadlec’s/ASPR’s operation as a “bottleneck.” See email from P. Navarro to R. Kadlec (Mar. 19, 2020), attached hereto as Exhibit 31. This greatly angered Dr. Kadlec and his team, and led them to further marginalize Dr. Bright and to retaliate against him by pressing for his removal.
• B. Dr. Bright Clashed with HHS Leadership About the Shortage of COVID-19 Testing Materials.
  • • In addition to pushing HHS leadership to expand the mask supply, Dr. Bright also repeatedly urged HHS leadership to secure and expand the supply of COVID-19 testing materials, such as swabs to collect the virus specimen, Viral Transport Media (“VTM”) to transport the swabs to a laboratory, and chemical reagents to perform the test. On March 11, 2020, anticipating a shortage of these materials as testing ramped up around the country, Dr. Bright asked Mr. Adams for the SNS’s inventory of chemical reagent, swabs, and VTM. See email from R. Bright to S. Adams (Mar. 11, 2020), attached hereto as Exhibit 32. To Dr. Bright’s surprise, Mr. Adams informed him that the SNS did not stock these items, and did not offer to assist in procuring them.
    • The next day, on March 12, 2020, Dr. Bright attended a hearing before the House Oversight and Reform Committee on coronavirus preparedness and response. During the hearing, CDC Director Dr. Robert R. Redfield testified repeatedly that the real “challenge” associated with implementing a national testing strategy would be supplying the requisite laboratory technicians, laboratory equipment, swabs, reagents, and other supplies necessary to perform the tests that already were in the marketplace. Dr. Redfield told the Committee, “I want to really emphasize – we focus so much on the actual test – we have to focus now on the whole system to get that testing really rolled out.” In listening to Dr. Redfield’s testimony, Dr. Bright grew increasingly concerned that there would be a severe shortage of testing materials, including swabs, as testing increased nationwide.
    • While sitting behind Dr. Redfield in the Congressional Hearing, Dr. Bright immediately instructed BARDA staff, including Deputy Director of Diagnostics and Medical Devices Rosemary Humes, to find out more about potential shortages and to compile a list of swab manufacturers in the event they needed to shore up the U.S. supply. He also sent an email to Dr. Johnson and Dr. Disbrow stating, “I need details on reagents [in] short supply. And swabs in short supply.” See email from R. Bright to R. Johnson (Mar. 12, 2020), attached hereto as Exhibit 33. Dr. Johnson responded in part, “We heard you and are working on this. . . . everyone I’m talking to says there is no swab shortage[.]” Id. Dr. Disbrow likewise responded in part, “Two people have indicated that [information regarding a swab shortage] may not be correct. Who has stated that there is an issue[?]” See email from R. Bright to G. Disbrow (Mar. 12, 2020), attached hereto as Exhibit 34. Despite Dr. Johnson’s and Dr. Disbrow’s skepticism about the impending shortages, Dr. Bright persisted. He told them, “They [at the CDC] are referencing shortage of reagents. Shortage of swabs. Shortage of people in the labs,” and urged them, “Forget about shortage terminology. What swab options do we have[?] Where are they made?” Id.
    • Early on the afternoon of March 12, 2020, Ms. Humes informed Dr. Bright that the CDC had “confirmed that some [testing] sites are reporting that supplies are getting low,” but that the FDA had assigned the matter to a “shortages team,” and the team did not anticipate a shortage of swabs because the two primary manufacturers had “huge manufacturing capacity.” See email from R. Humes to R. Bright (Mar. 12, 2020), attached hereto as Exhibit 35. Dr. Bright and Dr. Disbrow then called FDA Director of the Center for Devices and Radiological Health, Dr. Jeffrey Shuren, to learn where the FDA purchased its swabs. To Dr. Bright’s dismay, Dr. Shuren informed them that the FDA purchased its swabs from a manufacturer located in the Lombardy region of Italy – the epicenter of Italy’s coronavirus outbreak which had been placed under lockdown to prevent the spread of the virus. Dr. Bright and Dr. Disbrow immediately contacted the DOD Defense Threat Reduction Agency (“DTRA”), which assisted BARDA with the transport of vaccines from Germany to the U.S. during the Ebola epidemic, to determine whether military flights could be used to transport swabs from Italy to the U.S. in the event that commercial planes could not because of the lockdown. See email from D. Wolfe to G. Disbrow, (Mar. 12, 2020), attached hereto as Exhibit 36.
    • Early the next morning, on March 13, 2020, DOD DTRA Deputy Division Chief Major Jeffrey Froude informed Dr. Disbrow that a request for military assistance with transporting the swabs “likely . . . will need to come from [Secretary Azar] through official channels given the complexities of this mission and location restrictions compared to the previous [Ebola] mission.” See email from J. Froude to D. Disbrow (Mar. 13, 2020), attached hereto as Exhibit 37. Later that morning, DTRA Director of Chemical and Biological Technologies Dr. Ronald Hahn confirmed, “[A] direct request from SEC HHS to SEC DEF would get this at the appropriate level for decision and quick execution.” Id. Anticipating Dr. Kadlec’s resistance to this plan given his hostility toward Dr. Bright’s prior efforts to shore up the U.S. mask supply, Dr. Disbrow responded, “Th[is] definitely complicates the matter. We will continue to determine the [swab manufacturer’s] ability to obtain air freight from commercial [carrier].” Id. In the event that he and Dr. Bright were not able to secure Secretary Azar’s approval to partner with DOD, Dr. Disbrow also reached out to the SNS about its ability to assist with transporting the swabs. See email from G. Disbrow to S. Adams (Mar. 13, 2020), attached hereto as Exhibit 38. That same day, Dr. Bright sent an email to Mr. Navarro to let him know that BARDA had “discussed [VTM] and swab issues with FDA” and was reviewing several options to “reduce stress on global supply chain.” See email from R. Bright to P. Navarro (Mar. 13, 2020), attached hereto as Exhibit 39. In his email, Dr. Bright stated, “We need to reduce our vulnerability of accessing these critical materials [such as swabs and VTM] from outside the US. These little things that no one thinks about are killing us.” Id.
    • As Dr. Disbrow rightly predicted, Dr. Kadlec was resistant to even discussing the swab transport plan that he and Dr. Bright were trying to arrange with DOD. During an ASPR leadership call that afternoon, Dr. Bright attempted to brief Dr. Kadlec on the imminent swab shortages and critical need to find alternate transportation in the event that commercial planes could not fly to Italy because of the lockdown. Dr. Kadlec aggressively shot him down and in a hostile tone said, “I don’t care about swabs. I don’t want to hear about swabs. Move on.” Even after Dr. Disbrow told Dr. Kadlec that they had secured an option to fly military planes into Italy if they were able to obtain Secretary Azar’s approval, Dr. Kadlec refused to discuss the matter. Since Dr. Bright and Dr. Disbrow would need Dr. Kadlec’s support to seek the Secretary’s approval for the military flights, they seemingly had reached a dead end that could have had dire public health consequences.
    • Determined to secure a safe, reliable air bridge to Italy before the U.S. experienced a critical shortage of testing swabs, Dr. Bright turned to Mr. Navarro, his ally in the White House. On March 14, 2020, Dr. Bright emailed White House Senior Policy Advisor Christopher Abbott, a member of Mr. Navarro’s staff, to facilitate communication with Secretary of Defense Mark Esper about approving the military flights through the DOD. See email from R. Bright to C. Abbott (Mar. 14, 2020), attached hereto as Exhibit 40. Mr. Navarro’s office worked quickly and secured Secretary Esper’s approval in a matter of hours. Approximately two hours later, Maj. Froude confirmed that DTRA was “working to have a flight in the air as soon as tomorrow night.” Later that evening, Dr. Bright emailed Mr. Navarro, “You did something miraculous tonight to break through the wall and bureaucratic barrier that was stalling shipment from Italy to US. Four days of bureaucracy that you broke down in 5 minutes.” See email from R. Bright to P. Navarro (Mar. 14, 2020), attached hereto as Exhibit 41. Dr. Bright also asked rhetorically, “Why do we buy our critical supplies such as swabs from Italy instead of US producers[?] . . . In a global crisis, global supplies quickly become global shortages. Solution: Incentivize expansion of US produced ancillary medical supplies. Buy American to sustain the US capacity.” Id.
    • As a result of Dr. Bright’s persistence in the face of Dr. Kadlec’s hostility and opposition to his and Dr. Disbrow’s plan, BARDA’s partnership with the military has been able to transport 25 million swabs to the United States to address the dire shortage of this critical medical supply. The swab transport has now transitioned from the military operation to commercial cargo flights on Fed Ex and continues today between Italy and the U.S. to deliver swabs for use in testing facilities across the country. Unfortunately for Dr. Bright, however, his actions also increased Dr. Kadlec’s growing hostility toward him and his frustration over Dr. Bright’s insistence that HHS secure the U.S. supply of masks and other critical materials to combat the ongoing coronavirus pandemic.
• C. Dr. Kadlec and his staff increasingly circumvented Dr. Bright and BARDA in order to direct money without regard to scientific merit.
  • • When COVID-19 emerged as global health threat, Dr. Bright anticipated that BARDA, NIH, CDC, FDA, and DOD would all be inundated with proposals. To streamline the process and maximize efficiency, Dr. Bright created an interagency Medical Countermeasures Task Force (“MCM TF”) consisting of subject matter experts from each government agency to review COVID-specific science and requests for funding on an expedited and collaborative basis. This centralized, interagency process was set up to enable companies to discuss their science and data with multiple agencies at once and to enable the federal government to move quickly to identify and support proposals with the greatest potential to combat COVID-19. Dr. Bright announced the MCM TF and its dedicated online submissions portal, which was managed by BARDA, to over 1,400 participants on a call on January 30, 2020. [21 At the time of Dr. Bright’s involuntary transfer, more than 2,300 MCM TF proposals had been submitted to the special portal.]
    • In late February 2020, Dr. Disbrow and Dr. Johnson informed Dr. Bright that Mr. Clerici and the CEO of Drug Innovation Ventures at Emory University, Dr. George Painter, who previously had sought funding for EIDD-2801 as a “cure all” drug on the basis of extremely limited pre-clinical data, were once again seeking funding for the drug – this time, as a treatment for COVID-19. Instead of submitting a funding request to the MCM TF, however, Dr. Painter and Mr. Clerici contacted ASPR Strategic Innovation and Emerging Technology Manager Joe Hamel, a personal friend of Dr. Kadlec’s and the head of ASPR Next, an opaque funding program within ASPR that was established in August 2019 to fund products, equipment, and technology to assist with healthcare emergencies. This concerned Dr. Bright for several reasons. First, to Dr. Bright’s knowledge, Emory still had not completed the clinical trials for which it had received nearly $30 million in NIH and DOD funds. See supra section II.D. Therefore, technical experts lacked what they needed to evaluate the drug and ensure that it was safe. Second, Dr. Painter and Mr. Clerici were deliberately circumventing the MCM TF submissions process designed to streamline COVID-specific funding requests. Third, Dr. Painter and Mr. Clerici were requesting funding for a drug, EIDD-2801, from a program, ASPR Next, which was designed to fund products, equipment, and technology and did not have the resources or technical expertise to fund drug development.
    • As Dr. Bright investigated this issue further, BARDA Director of Contracts Management and Acquisitions, Joffrey Benford, advised him that some companies attempted to circumvent BARDA’s (or the MCM TF’s) rigorous scientific and contractual review process by submitting requests for funding to ASPR Next, which seemed to require only a few paragraphs of information as compared with the robust submissions required by BARDA. Further, ASPR Next did not appear to limit its consideration to proposals for products, equipment, and technology, as it was designed to do. Once an ASPR CO approved an ASPR Next proposal for funding, Joffrey learned that the CO would simply attempt to transfer it to a BARDA CO with instructions to fund the proposal – sometimes, with BARDA funds. Dr. Bright and his deputies consistently instructed BARDA COs not to fund proposals that had not been submitted to BARDA solicitations, been reviewed by  BARDA (MCM TF) subject matter experts, or had gone through the full scientific and business proposal vetting process. However, it was becoming increasingly clear to Dr. Bright and others that Dr. Kadlec and Mr. Hamel were using ASPR Next to circumvent the BARDA review process and to fund their “pet” projects, regardless of scientific merit. Dr. Bright’s efforts to safeguard the review process were doing little more than escalating tensions with Dr. Kadlec and members of his leadership team.
    • On April 2, 2020, HHS Deputy Chief of Staff for Policy Paul Mango telephoned Dr. Bright to discuss the status of several funding proposals that Mr. Mango said had been submitted to ASPR Next, including one submitted by Ridgeback Biotherapeutics LP (“Ridgeback”). Dr. Bright told Mr. Mango that he did not know the status of any of the proposals but would find out what he could from Mr. Hamel. Later that morning, Dr. Bright sent an email to Mr. Hamel requesting information about “the process ASPR Next is using to solicit, review and respond to proposals,” especially those related to COVID-19, so that they could “remain fully aligned as the pressure to succeed and report out continues to grow.” See email from R. Bright to J. Hamel (Apr. 2, 2020), attached hereto as Exhibit 42. Dr. Bright also requested information about the number of ASPR Next’s submissions, the categories of those submissions, and the number of awards made and pending on a “regular interval,” in order to keep Mr. Mango and their other colleagues informed about the program’s activities. Id.
    • Later that afternoon or the following day, having not received a response from Mr. Hamel, Dr. Bright called ASPR Chief Science Advisor, Dr. Chris Hassell, in an effort to learn more about ASPR Next’s internal processes. Dr. Bright told Dr. Hassell about his phone call with Mr. Mango and asked what he knew about ASPR Next. Dr. Hassell told Dr. Bright that he did not know much about the program, but that it appeared to him that Mr. Hamel was “running his own enterprise” at ASPR Next with Dr. Kadlec’s tacit approval. Dr. Hassell also told Dr. Bright that Dr. Kadlec frequently took phone calls directly from industry partners and agreed to fund their proposals without following the requisite review processes. Dr. Hassell said that he had even discussed the issue with ASPR Principal Deputy Assistant Dr. Keven Yeskey, who was “angry” about ASPR Next’s deviation from the requisite contracting protocol. Dr. Hassell disclosed that he sought to keep his distance from ASPR Next because he was concerned about its potentially illegal and unethical processes.
    • A few days later, on April 7, 2020, the CEO of Ridgeback, Wendy Holman, telephoned Mr. Benford, to discuss the funding proposal she had submitted to ASPR Next for a clinical trial that was scheduled to begin the following day. As Mr. Benford later learned, Ridgeback had partnered with Emory on EIDD-2801 development, and the two were working together to secure funding. Ms. Holman told Mr. Benford that Mr. Shuy had directed her to work with him (Mr. Benford) to secure approximately $100 million in pre-award funding because ASPR Next contracting staff were overwhelmed. As Ms. Holman stated in an email to Mr. Benford later that day, Dr. Kadlec had called her the previous evening to ask her to “accelerate [the clinical trials] as fast as possible.” See email from W. Holman to J. Benford (Apr. 7, 2020), attached hereto as Exhibit 43. The next day, Mr. Shuy directed Mr. Benford to fund the Ridgeback proposal as quickly as possible, and preferably within 24 hours.
    • Mr. Shuy’s directive raised several significant concerns about the award process. First, acquisition procedures for a contract award of Ridgeback’s size required in-depth analyses that would take at least 10-20 days to complete. Second, Ridgeback had not followed the proper procedure for receiving BARDA funding. It failed to submit a BAA white paper or full proposal to the BARDA BAA. In fact, Ridgeback had not provided BARDA with any documentation of its request for funding. Third, a time-sensitive procurement of this size would strain BARDA’s personnel resources, slowing down critical activities for COVID-related projects that had already received BARDA approval. Mr. Benford enumerated these concerns in an email to ASPR HCA Schuyler Eldridge on April 13, 2020. See email from J. Benford to S. Eldridge (Apr. 13, 2020), attached hereto as Exhibit 44. Ultimately, Mr. Benford forced Ridgeback to adhere to BARDA’s rigorous review process. The award was not made prior to Dr. Bright’s departure from BARDA.
    • As made explicit in email exchanges, Dr. Kadlec and his subordinates viewed Dr. Bright as an obstacle to their efforts to move BARDA money around. With the subject line, “Shameless,” Dr. Hassell emailed Dr. Kadlec on March 14, 2020 about DOD researchers’ request that Dr. Kadlec fund a list of projects with money from BARDA: “That was a shameless attempt to circumvent [the Office of the Secretary of Defense] and BARDA and appeal to you directly to fund [DOD projects].” See email from C. Hassell to R. Kadlec (Mar. 14, 2020), attached hereto as Exhibit 45. Dr. Hassell’s email explained that some of these projects were already submitted to MCM TF, and went on to state that the labs DOD is seeking to fund are “in trouble for shady dealings, illegal accounting, and lack of accountability.” Id.
    • Yet instead of suggesting that ASPR deny DOD’s request for funding, Dr. Hassell explicitly offered to help ASPR work around Dr. Bright to obtain the necessary approval. Referring to Dr. Bright by name (in an email on which he inadvertently copied Dr. Bright), Dr. Hassell wrote: “I know we have some issues with Rick,” then offered to talk with BARDA staff within the Division of CBRN (chemical, biological, radiological and nuclear threats) Medical, whom Dr. Hassell described as “straight shooters.” Dr. Hassell concluded the email by insisting he will “keep [Dr. Kadlec] legal.” Id. Over the next few days, Dr. Hassell discussed DOD funding requests with various BARDA staff, working around Dr. Bright in the process. The projects in question totaled over $100M.
• D. Dr. Kadlec’s animus toward Dr. Bright escalated markedly when Congress for the first time appropriated money directly to BARDA, making it harder for him to siphon off and control BARDA’s funds.
  • • In early to mid-March 2020, HHS legislative officers received requests for Dr. Bright and Dr. Disbrow to brief various members of Congress and staff, including from the House Appropriations Committee, regarding BARDA’s efforts to combat COVID-19, which they did. At the same time, Dr. Bright received calls directly from members of Congress or their staff, including from Senator Steve Daines (R-MT), Senator Chris Coons (D-CT), Senator Roy Blunt (R-MO), Congresswoman Anna Eshoo (D-CA) and a staff member in the office of Congresswoman Rosa DeLauro (D-CT). During each of these conversations, Dr. Bright explained how BARDA used its funds to aggressively support possible COVID-19 treatments, diagnostics, and vaccines. He also explained that BARDA had not been able to move as quickly as he would have liked because it lacked money, experienced delays in accessing funding once appropriated, and was receiving more proposals than it could fund. Dr. Bright also explained that HHS and ASPR had siphoned off some of the money Congress had designated for drug and vaccine development, leaving BARDA in a position where it had to plead with Dr. Kadlec and Secretary Azar for the money it needed to do its job.
    • On March 20, 2020, Dr. Bright spoke with Senator Daines about BARDA’s efforts to combat the pandemic. Senator Daines emphasized the importance of BARDA’s work, and said something to the effect of, “The last thing we want to do is have you worry about money when you should be focusing on science.”
    • Around this same time, Dr. Kadlec learned of the possibility of a direct congressional appropriation to BARDA, rather than through HHS/ASPR, and he was furious. On March 20, he emailed Dr. Bright: “BTW did you ask Eshoo to find (sic) BARDA over ASPR?!” See email from R. Kadlec to R. Bright (Mar. 20, 2020), attached hereto as Exhibit 46. In response, Dr. Bright explained that earlier that day, Senator Daines asked BARDA “for a huge back of envelope estimate to pull out all stops for vaccine and drugs,” and he “[w]ants a huge number by this afternoon.” Id. Dr. Bright said that Dr. Disbrow and Dr. Johnson were working on preparing these estimates. One minute later, Dr. Kadlec responded, “Shuy needs to review ALL such estimates and submissions.” Id. Dr. Bright replied that he understood, and that Dr. Disbrow would be sending an estimate soon. Mr. Shuy then separately asked to connect with Dr. Bright “offline.” He instructed Dr. Bright, “Do not reach back out to these [congressional] offices or staff at this time.” Id.
    • On March 27, 2020, Congress passed and President Trump signed the Coronavirus Aid, Relief, and Economic Security (“CARES”) Act, Pub. L. 116–136. The Act appropriated $3.5 billion directly to BARDA for expenses related to the manufacturing and production of vaccines, therapeutics, and diagnostics responsive to COVID-19. To Dr. Bright’s knowledge, this was the first time Congress appropriated money directly to BARDA and it was a game changer. [22 Previously, Congress appropriated money to HHS, and the Secretary of HHS managed the availability and distribution of the funding. Prior to passage of the CARES Act, the HHS Assistant Secretary for Financial Resources (“ASFR”) was able to transfer funds to the ASPR, who in turn could transfer funds to BARDA. To receive money, BARDA had to submit a spending plan to Dr. Kadlec’s budget officer, Jay Petillo, who in turn submitted the plan to the ASFR. Through this process, Dr. Kadlec had complete control over BARDA’s money, and the ASFR oversaw the overall budget process for the department. Accordingly, both the Secretary of HHS and the ASPR, Dr. Kadlec, could control how much money BARDA received and when they received it, and also had the authority to transfer money out of BARDA’s account. In fact, on multiple occasions, Dr. Kadlec directed Mr. Petillo to transfer money out of BARDA’s account, often to the SNS or to support projects for ASPR Next, despite Dr. Bright’s objections. See e.g., section II(B), supra.]  For the first time, the ASPR had less control over BARDA’s money, and BARDA could direct its resources towards those proposals with the greatest scientific potential to combat COVID-19. Accordingly, it became much more difficult for Dr. Kadlec to redirect funds to support projects for his cronies or for political purposes. Dr. Kadlec obviously understood this fact and was not happy. After the passage of the CARES Act, Dr. Bright did not see or speak with Dr. Kadlec until three days later, on March 30, 2020. On that date, Dr. Bright entered Dr. Kadlec’s office at FEMA headquarters and attempted to update him on a new initiative being planned to rapidly enable a serology/antibody testing program. Dr. Kadlec sat in a chair working on his laptop and did not look up. Dr. Bright nevertheless provided Dr. Kadlec with an overview of the program and mentioned a potential briefing to Secretary Azar that evening or the next day. Dr. Kadlec responses were monosyllabic – “ok” “sure” “ok”. He never looked up from his computer and his demeanor was dismissive and disrespectful.
• E. Dr. Kadlec tried to bypass Dr. Bright to access BARDA money over Dr. Bright’s objections.
  • • On March 20, 2020, Dr. Kadlec wrote to the Executive Vice President of Research at Northwell Health, Dr. Kevin Tracey, to request an expedited review of the company’s clinical trial to develop a COVID-19 treatment. See letter from R. Kadlec to K. Tracey (Mar. 20, 2020), attached hereto as Exhibit 47. Northwell Health was working with Alchem Laboratories (“Alchem”) on a treatment using hydroxychloroquine in combination with famotidine, the active compound in the heartburn drug Pepcid AC. Dr. Kadlec invited Northwell Health to submit a proposal to ASPR Next and, in an unprecedented move, instructed it to “work with COVID clinical expert, Dr. Michael Callahan, in the preparation of this white paper and draft budget.” Id. Dr. Callahan is a consultant on Dr. Kadlec’s staff who was hired to advise HHS about the government’s COVID response. He is not a government employee. Yet as a consultant “who is advising or has advised the Federal Government with respect[] to a Federal agency procurement,” Dr. Callahan is prohibited from disclosing information about a contractor bid or proposal, or source selection information, before the award of a Federal agency procurement contract. See 41 U.S.C. § 2102(a)(3)(A). By directing a member of his staff to work as an agent of both the company and the government regarding the proposal, Dr. Kadlec was inviting violations of federal procurement law.
    • On March 31, 2020, Dr. Tracey emailed a proposal and budget to Dr. Kadlec for Northwell Health, also confirming that he had worked with Dr. Callahan to prepare the submission for BARDA. [23 See Brendan Borrell, New York Clinical Trial Quietly Tests Heartburn Remedy Against Coronavirus, SCIENCE (Apr. 26, 2020), available at https://www.sciencemag.org/news/2020/04/newyork- clinical-trial-quietly-tests-heartburn-remedy-against-coronavirus (detailing Dr. Callahan’s simultaneous work with Dr. Kadlec and Northwell Health to obtain BARDA award).] Dr. Tracey copied Secretary Azar, and other HHS senior officials, but not Dr. Bright on this email. See email from K. Tracey to R. Kadlec (Mar. 31, 2020), attached hereto as Exhibit 48. Within an hour, Dr. Kadlec responded in part: “I have actioned this with BARDA [sic] Michael Callahan will follow up.” Id. Although Dr. Kadlec communicated with Dr. Disbrow about the proposal, he did not notify Dr. Bright.
    • Dr. Bright learned about this proposal when someone on the email exchange forwarded the messages to him, Dr. Disbrow, and others, along with the note: “FYSA – no one from BARDA or the MCM TF is copied on this plan for an expanded access Clinical Trial, but they are asking if it will be transferring to BARDA after award by ASPR Next.” Id. On or around April 1, 2020, Dr. Disbrow called Dr. Bright with concerns about this request. Dr. Disbrow asked Dr. Bright, “Can you believe they want to use Pepcid AC now?” Dr. Disbrow noted that this was a “Callahan thing.” Dr. Bright told Dr. Disbrow that Dr. Callahan’s involvement seemed to be a conflict of interest, and Dr. Disbrow agreed. Afterward, Dr. Bright called Dr. Linda Lambert, who oversees the BARDA clinical team, to discuss his concerns about this contract proposal and Dr. Callahan’s role in assisting companies with their contract submissions. Dr. Lambert was also concerned about the contract proposal, and agreed with Dr. Bright that Dr. Callahan’s involvement was a conflict of interest. Dr. Bright instructed Dr. Lambert to ensure that BARDA had a clinical review of this drug. On April 1, 2020, Dr. Disbrow sent an email directing relevant BARDA employees to “pause on further emails since no actual proposal has been submitted.” See id.
    • Three days later, Dr. Kadlec again excluded Dr. Bright when he emailed senior BARDA officials directing the award of BARDA funds to Northwell Health. On April 4, 2020, Dr. Kadlec sent an email to Dr. Disbrow and Dr. Lambert encouraging them to move forward with the proposal: “Gary and Linda just following up on this and making sure we support this trial. I understand there was some follow up to determine the exact cost of this. But would like to close the loop on this.” See email from R. Kadlec to G. Disbrow (Apr. 4, 2020), attached hereto as Exhibit 49. On April 14, 2020, BARDA awarded Alchem a $20.7 million contract for work to be performed by Northwell Health. Dr. Bright, the BARDA Director, was entirely excluded by Dr. Kadlec from the award process on this contract.
    • This contract was just one more example of Dr. Kadlec’s actions in bypassing all rules and procedures designed to ensure public safety and to avoid corruption in the award of billions of dollars in government funds. Indeed, Dr. Kadlec cultivated an environment in which industry partners regularly bypassed agency procedures designed to prevent influence peddling and conflicts of interest, forcing Dr. Bright and his deputies to spend valuable time—including during the ongoing COVID-19 health crisis—fending off improper and often illegal requests from private industry and their agents.
    • Most recently, on April 10, 2020, Novavax CEO Stanley Erck called Dr. Bright’s office requesting to speak directly with Dr. Bright about Novavax’s proposal for a COVID-19 vaccine. Since Novavax had already submitted a BAA white paper about the vaccine, federal law clearly prohibited Dr. Bright from speaking with him about the company’s proposal. Dr. Bright’s Special Assistant therefore informed Mr. Erck that BARDA could not discuss the proposal at that time. Undeterred, three days later on April 13, 2020, Novavax Senior Vice President of Public Policy and Commercial Strategy Brian Rosen circumvented Dr. Bright’s office entirely and sent an email directly to Dr. Kadlec. In his email, Mr. Rosen touted Novavax’s history of working with coronaviruses, provided information about “recent milestones” in the company’s development of its COVID-19 vaccine, and lauded the vaccine as “one of the earliest and most promising.” He also requested an opportunity to speak with directly with Dr. Kadlec about the company’s proposal. See email from B. Rosen to R. Kadlec (Apr. 13, 2020), attached hereto as Exhibit 50.
    • Soon after learning about Novavax’s second attempt to circumvent federal law and speak with Dr. Bright or Dr. Kadlec, Dr. Disbrow emailed Dr. Hassell, Dr. Houchens, and Dr. Bright stating in part, “we cannot have discussions with [Novavax] with respect to their [BAA white paper] submission. All submissions will be reviewed by the [MCM TF] for prioritization.” Id. Dr. Bright responded that “[d]ue to the nature of having an open proposal in house, I strongly encourage you [Mr. Hassell] to coordinate with the ASPR [Head of Contracting Activity (“HCA”)], Schuyler Eldridge, to determine the best way to handle this call with ASPR.” [24 As the ASPR HCA, Mr. Eldridge is charged with enforcement of the federal law at issue, the Procurement Integrity Act (“PIA”).] Id. In stark contrast to the approach of Dr. Bright and Dr. Disbrow, and despite the fact that speaking with Mr. Erck or Mr. Rosen about Novavax’s pending submission was a blatant violation of federal law, Dr. Kadlec responded to Mr. Rosen’s email that he was “looking forward to” speaking with him. See email from R. Kadlec to B. Rosen (Apr. 13, 2020), attached hereto as Exhibit 51. Dr. Bright, who received notice of his removal just four days later, does not know whether Dr. Kadlec ultimately spoke to Novavax about its proposal but assumes that he did so. This of course warrants further inquiry.
    • F. Dr. Bright resisted pressure from HHS leadership to make potentially harmful drugs widely available, including chloroquine and hydroxychloroquine, and provided information to a reporter about the specific danger to the public health and safety caused by the Administration’s decision to release these untested drugs for use by the general public.
    • In an apparent effort to score a short-term political victory for the Administration during the escalating health crisis, the Office of the ASPR pressured BARDA to promote the malaria drug chloroquine as a therapeutic for COVID-19, despite a clear lack of scientific support. On March 10, 2020, ASPR Chief of Staff Shuy emailed Dr. Johnson, who was head of BARDA’s Division of Influenza and Infectious Diseases, to ask whether BARDA was considering chloroquine as a therapeutic for COVID-19. See email from B. Shuy to R. Johnson (Mar. 10, 2020), attached hereto as Exhibit 52. Under BARDA’s COVID-specific contract approval process, Dr. Johnson was then serving as SSA with final approval over BARDA’s COVID-19 related contracts with private industry. Dr. Johnson responded to Mr. Shuy that the MCM TF was monitoring clinical trials of the drug, but it was not enthusiastic about chloroquine’s use as a therapeutic. Specifically, Dr. Johnson told to Mr. Shuy that although the drug “has been shown to have in vitro effects on other microbes . . . that has not panned out to clinical benefit” for COVID-19 patients. Id.
    • On March 17, 2020, and without explanation, Mr. Shuy demanded an update from Dr. Johnson about the use of chloroquine as a therapeutic for COVID-19. Mr. Shuy wanted the information “ASAP . . . like immediately [.]” Id. Dr. Johnson responded by reiterating the scientific basis for the MCM TF’s lack of enthusiasm about the drug – i.e., the data to date was not compelling – but assured Mr. Shuy that the MCM TF was closely monitoring several ongoing clinical trials of the drug. Id. That afternoon, Joseph Hamel, ASPR Strategic Innovation and Emerging Technology Manager, emailed BARDA Acting Director of CBRN Medical Countermeasures and lead for the COVID-19 MCM TF, Dr. Christopher Houchens, and several ASPR officials stating that an outside group had approached the ASPR about a “promising compound” for the treatment of COVID-19: chloroquine. See email from J. Hamel to C. Houchens (Mar. 17, 2020), attached hereto as Exhibit 53. According to Mr. Hamel, Bayer AG (“Bayer”) had offered to donate three million chloroquine pills to the SNS. Mr. Hamel directed Dr. Houchens to have his team “take a look” at safety information provided by Bayer to “make sure it’s legit.” Id. Mr. Hamel closed his email by stating, “This can be a BIG immediate win.” Id. (Emphasis added).
    • Unfortunately, the scientific evaluations did not support the utility of the Bayer donations. Later on March 17, 2020, Dr. Houchens emailed Dr. Bright with his team’s review of Bayer’s chloroquine safety information. See email from C. Houchens to R. Bright (Mar. 17, 2020), attached hereto as Exhibit 54. The email communicated his team’s opinion that “there are safety liabilities associated with the drug . . . accepting the donation could send a signal that we are not concerned about the risk.” Id. (Emphasis added). He stasted: “I do not believe we should accept the donation [of chloroquine from Bayer] until we have an understanding on the clinical utility of the drug. Accepting the donation could lead to widespread use that is not supported by any clinical data.” Id. (Emphasis added). Dr. Houchens noted that “not a single study has posted any data for peer-review” and he emphasized that “[w]e need to be very careful about the message it sends the public about accepting a donation of a drug with questionable utility . . . .” Id.
    • Dr. Bright received a similar message from BARDA Chief of Therapeutics for Influenza and Emerging Infectious Diseases and Lead for the COVID-19 therapeutics working group within MCM TF, Dr. Kimberly Armstrong, who stated that the consensus among BARDA and FDA scientists was to wait for additional clinical data before making any recommendations on the use of chloroquine to treat COVID-19. See email from K. Armstrong to R. Bright (Mar. 17, 2020), attached hereto as Exhibit 55. Dr. Armstrong expressly stated that there was “no data available to support that chloroquine provides clinical benefit in the treatment or prevention of COVID-19.” Id. (Emphasis added).
    • The next day, March 18, 2020, Dr. Bright wrote Mr. Hamel that it remained “unclear what ASPR has in mind with this donation plan” and requested from Mr. Hamel “all information and data received” about the Bayer donation and “all prior discussions” with Bayer. See email from R. Bright to J. Hamel (Mar. 18, 2020), attached hereto as Exhibit 56. Mr. Hamel told Dr. Bright to direct any questions to Mr. Shuy, who he said was “running point” on coordinating the donation with Secretary Azar and Bayer. Id. Also on March 18, 2020, Mr. Hamel emailed Dr. Johnson and SNS officials at ASPR that he had “[j]ust got[ten] the call from Bryan [Shuy]” and it was “[t]ime to move” on obtaining an Emergency Use Declaration. See email from J. Hamel to R. Johnson (Mar. 18, 2020), attached hereto as Exhibit 57. An Emergency Use Declaration enables the FDA to issue an Emergency Use Authorization (“EUA”), which allows unapproved drugs, or unapproved uses of approved drugs, to be used in an emergency when there are no adequate, approved, and available alternatives. A chloroquine EUA would make the drug available for the treatment of COVID-19 under a physician’s supervision in a hospital setting. That afternoon, and prior to the ASPR’s official approval, Axios reported that Bayer was preparing to donate “a large supply of an older malaria drug,” chloroquine, to the SNS. [25 Caitlin Owens, Scoop: Bayer to Donate Potential Coronavirus Drug to U.S., AXIOS (Mar. 18, 2020), available at https://www.axios.com/scoop-bayer-to-donate-potential-coronavirus-drug-to-uscc8c1a5a- 6a14-4e36-8b07-07eccf4eff36.html.]
    • The next day, on March 19, 2020, Bayer announced that it had “in recent days . . . been in talks with the White House, HHS, CDC, and the FDA” and planned to “join[] the U.S. government’s fight against COVID-19” by donating three million tablets of chloroquine to the SNS. [26 Bayer Partners with U.S. Government on Major Product Donation to Fight Coronavirus, BAYER (Mar. 18, 2020), available at https://bayer2019tf.q4web.com/news/news-details/2020/Bayer- Partners-with-US-Government-on-Major-Product-Donation-to-Fight-Coronavirus/default.aspx.] The press release stated that chloroquine was FDA-approved for the prevention and treatment of malaria but had shown “limited” potential for the treatment of COVID-19. The press release also stated that Bayer was “working with appropriate agencies on an Emergency Use Authorization” so that the drug could be used to treat COVID-19 in the U.S. That same day, President Trump falsely stated during a White House press conference that clinical trials of chloroquine and/or hydroxychloroquine were producing “very, very encouraging early results” and promised the American public that his Administration was “going to be able to make [chloroquine and/or hydroxychloroquine] available almost immediately.” [27 See Remarks by President Trump, Vice President Pence, and Members of the Coronavirus Task Force in Press Briefing, WHITE HOUSE (Mar. 19, 2020), available at https://www.whitehouse.gov/briefings-statements/remarks-president-trump-vice-president-pencemembers- coronavirus-task-force-press-briefing-6/.]
    • Over the next several days, HHS, ASPR, and FDA facilitated the importation of Bayer’s donation of chloroquine from manufacturers and distributors in Pakistan and India and also sourced chloroquine and hydroxychloroquine from domestic manufacturers to shore up the U.S. supply. During this time, however, it remained unclear to Dr. Bright and others at BARDA how the drugs would be made available to the public, including which agency would sponsor the widely-publicized EUA.
    • On March 23, 2020, Dr. Bright received an urgent directive from HHS General Counsel Bob Charrow, passed down from the White House, to drop everything and make the chloroquine donated by Bayer widely available to the American public. Mr. Charrow told Dr. Bright that Secretary Azar was directing BARDA to establish a Nationwide Expanded Access Investigational New Drug (“IND”) protocol for chloroquine, which would provide significantly greater access to the drug than would an EUA. Mr. Charrow told him that the protocol was to include a new database or application created by Oracle to assist in determining who got the medicine and to allow patients to enter their symptoms into an app in lieu of seeing a physician while taking the drug. Unlike an EUA, a Nationwide Expanded Access IND protocol would make the drug available for the treatment of COVID-19 outside a hospital setting and without close physician supervision. According to Mr. Charrow, Secretary Azar was issuing the directive to accommodate both the Bayer donation of chloroquine tablets and a soon-to-be-announced donation by Oracle co-founder Larry Ellison of an online platform about which Mr. Charrow could provide few details. Media reports from the time period indicate that Mr. Ellison, a prominent Trump donor, helped convince President Trump that chloroquine and hydroxychloroquine could effectively treat COVID-19. [28 See, e.g., Yasmeen Abutaleb, et al., Oracle to Partner with Trump Administration to Collect Data on Unproven Drugs to Treat COVID-19, WASH POST (Mar. 24, 2020), available at https://www.washingtonpost.com/politics/oracle-to-partner-with-trump-administration-to-collect-data-on-]
    • Mr. Charrow also told Dr. Bright that he had personally drafted the informed consent form required for the Expanded Access IND protocol and wanted BARDA to set up this program within the next two days. Mr. Charrow further advised Dr. Bright that the donated drug was to be deposited in the SNS for distribution to Americans. Dr. Bright later learned that neither the foreign drug production facilities, nor the pills, had been inspected by the FDA or approved for safe use in the United States.
    • Secretary Azar’s directive concerned Dr. Bright for several reasons: first, the best scientists and clinicians in HHS had advised that data on chloroquine and hydroxychloroquine was insufficient to know if these drugs had any clinical benefit in COVID-19 patients; second, there were known safety concerns associated with these drugs, including dangerous irregular heart rhythms and even fatalities—risks that could increase if the drugs were used in combination with other drugs, including some antibiotics; and third, inconsistent and often dangerous lapses in quality control in some non-FDA inspected drug production facilities raised concerns of potential toxicity posed by contaminants and uncontrolled levels of active ingredients in imported medicines. Given the growing panic over the COVID-19 pandemic, the desperation to find a cure, and the irresponsible public promotion of an unproven medicine, Dr. Bright was extremely concerned about the prospect of chloroquine being made readily available to the public, without close patient monitoring by medical professionals. HHS scientists repeatedly agreed that the best path forward would be to evaluate chloroquine and hydroxychloroquine through randomized, placebo-controlled clinical trials (“RCT”), which were already underway.
    • Secretary Azar’s directive to secure a Nationwide Expanded Access IND protocol for chloroquine based on scant scientific evidence and on such a short timeframe sent Dr. Bright and his colleagues scrambling. Within the hour, Dr. Bright had called a meeting of Dr. Linda Lambert, Chief Medical Officer Dr. Robert Walker, Director of Regulatory and Quality Affairs Dr. Tremel Faison, and Drs. Johnson, Disbrow, and Houchens to discuss the directive. The group expressed serious concerns about a Nationwide Expanded Access IND protocol for chloroquine given the lack of clinical data available about its therapeutic benefits and concerns about its potential safety risks, especially if administered without close physician supervision. Dr. Bright and FDA colleagues were also concerned about the quality and potential toxicity of chloroquine supplies produced and shipped in from facilities in India and Pakistan that were not approved by the FDA, and were therefore not approved to be used in the U.S. marketplace. The HHS clinical and regulatory expert teams worked frantically for 48 hours without sleep to come up with a plan that would ensure the greatest level of safety for people who received this drug. They discussed narrower options for the rollout, including a small pilot study, and established an interagency working group of clinical and regulatory experts to determine the safest way to make the unproven drug available without causing harm to the American public.
    • Later that same day, March 23, 2020, FDA Chief Counsel Stacy Amin urged various HHS and FDA officials to move forward on the Expanded Access IND protocol for chloroquine to coincide with President Trump’s forthcoming announcement of his Administration’s partnership use-of-antimalarial-drugs-to-treat-covid-19/2020/03/24/ecbb8b76-6de2-11ea-b148- e4ce3fbd85b5_story.html. with Oracle. See email from S. Amin to R. Charrow (Mar. 23, 2020), attached hereto as Exhibit 58 (“Can we please start moving forward on BARDA sponsoring the chloroquine IND and NIH providing the IND (sic) ? The President is announcing this tonight and I believe the WH would like it set up by tomorrow with data to flow into the Oracle platform.”) Dr. Bright remained extremely concerned, as HHS leadership seemed willing to make these drugs widely available without any clinical assurance that the drug was safe. He feared that the wide scale availability of chloroquine and hydroxychloroquine could lead to serious patient harm and potentially many patient deaths.
    • In an email to Dr. Kadlec and several of Dr. Bright’s BARDA colleagues that evening, Dr. Bright expressed frustration with BARDA’s exclusion from the decision-making process, stating, “I am not sure who has the background on this, BARDA does not yet and [is] playing catch up with little to no details. . . . Who has talked with Oracle? Where is the drug coming from? Has FDA cleared?” Id. In response, Dr. Kadlec merely confirmed what Dr. Bright already knew: “Bob Charrow asked that BARDA lead this. Please identify a team to support.” Id.
    • That night, Dr. Bright emailed Ms. Amin stating that the details available to BARDA regarding an Expanded Access IND protocol for chloroquine remained “very sketchy,” even though the Secretary had directed BARDA to “move quickly.” See email from R. Bright to S. Amin (Mar. 23, 2020), attached hereto as Exhibit 59. He requested to speak with Ms. Amin “urgently” about the Secretary’s directive. Ms. Amin responded that the White House planned to discuss the following morning whether the protocol should be national in scale or piloted to New York first. Dr. Bright replied, in part: “Given the limited information we have on both the drug and the innovative data system, I’m sure we’d all lean heavily towards a pilot over a national rollout. Many variables to get right in an already hectic setting across the nation.” Id.
    • The next day, on March 24, 2020, the Director of the Center for Drug Evaluation and Research, Dr. Janet Woodcock, called Dr. Bright and strongly recommended that BARDA submit an application for an EUA instead of an Expanded Access IND protocol. Given the uncertainty about the risks of chloroquine, an EUA would better protect patients by enabling physicians to closely monitor their progress in a hospital setting and treat any side effects of the drug. Dr. Bright agreed with Dr. Woodcock that more limitations on these unknown drugs would be safer for the American public. A small Chinese clinical study released that same day, and which Dr. Bright discussed with Dr. Woodcock, produced statistically insignificant results about the therapeutic benefits of hydroxychloroquine and provided no more compelling reason to make the drug available nationwide without also requiring the close supervision of a physician when administered.
    • Over the next several days, Dr. Bright and Dr. Woodcock urged their colleagues on the clinical and regulatory teams implementing the Secretary’s directive to secure an EUA for chloroquine and hydroxychloroquine instead of a Nationwide Expanded Access IND protocol. Implementing the EUA was a compromise position, to rein in HHS leadership’s initial campaign to make the drugs available to the public outside of a hospital setting and without physician supervision. Dr. Bright and Dr. Woodcock ultimately prevailed upon their colleagues, and the FDA assisted BARDA in drafting an EUA request and provided it to Dr. Bright on the evening of March 28, 2020. Dr. Bright reviewed and edited the request letter to clarify that although he was being directed to sign the EUA request, it was not at his or BARDA’s behest. After Dr. Kadlec’s review and approval, the EUA request was sent to the FDA at 11:31p.m. on March 28, and at 12:03 a.m. on March 29, 2020, the FDA issued an EUA for chloroquine and hydroxychloroquine to be used by licensed health care providers to treat adults and teens hospitalized with confirmed COVID-19 who weigh more than 110 pounds, if they could not otherwise participate in a randomized controlled trial. This directive—which kept chloroquine and hydroxychloroquine in the hands of healthcare professionals, and out of the hands of the public at large—ensured that the drugs were administered to patients only under close physician supervision and who were known to be infected with the virus.
    • Despite the brokered compromise, the Administration nevertheless continued to push for expanded, unsupervised access to chloroquine and hydroxychloroquine, in blatant violation of the EUA issued by its own FDA and regardless of the risk to the American public. On April 4, 2020, hours after President Trump once again touted hydroxychloroquine as a treatment for COVID-19 during a White House press conference, HHS Assistant Secretary for Health Adm. Brett Giroir, M.D., instructed FEMA Administrator Peter Gaynor, Vice Director for Logistics of the Joint Chiefs of Staff Rear Adm. John Polowczyk, and Dr. Kadlec to mobilize the nation’s supply chain to “flood NY and NJ with treatment courses [of hydroxychloroquine].” See email from B. Giroir to S. Adams (Apr. 4, 2020), attached hereto as Exhibit 60. Admiral Giroir issued this instruction based on orders from the White House. Mr. Gaynor likewise had received instructions from FDA Commissioner Dr. Stephen Hahn to distribute hydroxychloroquine to pharmacies nationwide, even though the EUA did not provide for outpatient use of the drug.
    • When SNS Deputy Director Steven Adams cautioned Admiral Giroir that the EUA limits the use of chloroquine and hydroxychloroquine to the treatment of hospitalized patients, he responded, “NOPE . . . Needs to go to pharmacies as well. The EUA matters not . . . The drug is approved [and] therefore can be prescribed as per doctor’s orders. That is a FINAL ANSWER.” Id. (Emphasis added). Adm. Giroir’s response made crystal clear that the Administration would stop at nothing to make the experimental drug widely available to the American people, no matter the consequences—not because it was safe or effective, but because as ASPR’s Joe Hamel stated, it was seen by the Administration as “a BIG immediate win.”
    • At this point, Dr. Bright had exhausted all efforts to protect patients from the Administration’s embrace of hydroxychloroquine and chloroquine as a treatment for COVID-19. He believed the EUA he had brokered would limit the administration of the drugs to patients in a hospital setting and under the care of physicians. Yet the following week, the Administration, including the Dr. Kadlec, had continued to push chloroquine and hydroxychloroquine for widespread use in non-clinical settings and without physician supervision. Dr. Bright remained extremely concerned about the drug’s importation from Pakistan and India because the FDA had not inspected the drugs or the factory that produced them. In Dr. Bright’s experience, drugs from uninspected factories can be contaminated or dosed improperly, and this could obviously be dangerous to those who took the medication. Apparently unconcerned about this known danger, Dr. Kadlec and others in the Administration sought to “flood” the marketplace with these drugs. Dr. Bright and his staff voiced their concerns repeatedly, but the Administration was not interested in hearing from BARDA or the MCM TF—the subject matter experts. Dr. Bright and his team had apparently spent all their political capital in their effort to limit chloroquine and hydroxychloroquine to an EUA. Within HHS, there was no desire (outside of BARDA) to stop this speeding train. Dr. Bright felt powerless to protect the public from this potentially toxic chemical that HHS, at President Trump’s insistence, was touting as a safe treatment.
    • Yet he felt an urgent and compelling need to inform the American public that this drug with insufficient scientific data to support its use for COVID-19 patients, with known safety concerns, and with no FDA oversight over its quality was now being pushed or “flooded” onto the streets of America. At this point, Dr. Bright felt that the government had failed to adequately heed these warnings and to inform Americans of the source and serious risks posed by this donated drug. He believed that Americans needed to have this critical information available to them to before taking the medication.
    • It was at this time that a journalist left a message for Dr. Bright inquiring about the potential dangers of hydroxychloroquine and chloroquine. The journalist indicated that numerous government sources had expressed concerns about the donated chloroquine coming from unregulated factories in India and Pakistan, that there were significant risks associated with these drugs, and that the administration was rushing to get them into the hands of the American people. The journalist asked Dr. Bright to confirm this information. Dr. Bright considered the request carefully. He felt that he had exhausted all avenues to alert government officials that they were rushing into a potentially dangerous situation and that there was no one to help stop the push to “flood” the country with this unproven and potentially dangerous drug. He concluded that his only remaining avenue was to share his concerns with the journalist who understood the specific issue and risks associated with these drugs and who had already gathered substantial information from multiple sources.
    • In coming to this decision, Dr. Bright wrestled with what he felt was both a moral and a professional obligation to save lives and protect Americans. He knew that providing this information to a journalist would place him further at odds with HHS leadership. However as the death toll mounted exponentially each day, Dr. Bright concluded he was left with no choice, and he had a clear obligation to the American public, particularly those vulnerable as a result of illness from COVID-19, to protect it from drugs which he firmly believed constituted a substantial and specific danger to public health and public safety. Dr. Bright gave the journalist HHS emails that were not privileged or classified or otherwise legally restricted from dissemination, which discussed the drug’s potential toxicity and demonstrated the political pressure to rush the drugs from Pakistan and India to American households. [29 Dr. Bright’s disclosures to the journalist are protected under the Whistleblower Protection Act (“WPA”), 5 U.S.C. § 2302(b)(8)(A) (protecting employees who disclose information that reveals “any violation of any law, rule, or regulation,” or “a substantial and specific danger to public health or safety”); Department of Homeland Security v. MacLean, 574 U.S. 383, 393 (2015) (federal employee’s disclosures to reporter about dangerous agency activity were protected under Whistleblower Protection Act) (citing 5 U.S.C. § 2302(b)(8)(A)).] Dr. Bright hoped that by shining a light on HHS’s reckless and dangerous push to make these drug available, human lives would be saved. On April 15, 2020, with rumors of an upcoming article circulating at HHS, Mr. Shuy brought up “the media,” and specifically warned him to “be careful” about speaking to the media.
    • When an article later appeared that demonstrated the reckless actions of the Administration to release an unproven and potentially very dangerous drug, HHS leadership suspected that Dr. Bright was the source. The article did not reflect well on the Administration as it made clear that officials were well aware of the potentially serious issues with the drug but nevertheless viewed it as a political win. Following Dr. Bright’s removal as Director of BARDA and involuntary transfer, HHS officials told the media that Dr. Bright’s relationship with Dr. Kadlec had been frayed, but the “leak” was the straw that broke the camel’s back. [30 Sarah Owermohle, FDA Official Steps into Vaccine Vacuum after Shakeup, POLITICO (Apr. 29, 2020), available at https://www.politico.com/news/2020/04/29/fda-official-coronavirus-vaccine-220858.]
• G. Dr. Bright achieved significant success as Director of BARDA and his removal was blatantly retaliatory.
  • • On the morning of Friday, April 17, 2020, Dr. Bright briefed Senator Roy Blunt (R-MO) about BARDA’s work on vaccines and drugs to address the COVID-19 pandemic. Senator Blunt was particularly interested in BARDA’s diagnostic efforts, and Dr. Bright advised him about BARDA’s plans to invest first in big laboratories to augment CDC capabilities, then rapidly push technology to get diagnostics closer to patients, simplify the testing, and to reduce the time it takes patients to get results. He told the Senator about BARDA’s strategy that was created in mid- January to accelerate development of SARS-CoV-2 testing and its recent awards to companies developing home diagnostic tests and to companies developing both antigen and antibody tests— a key to getting Americans back to work. Senator Blunt was impressed with Dr. Bright’s briefing and told him that he was “proud” of Dr. Bright and of BARDA’s work under his direction. Senator Blunt surprised Dr. Bright by giving him his personal cell phone number and directing him to call him if he ever wanted to discuss diagnostics, efforts to fight COVID-19, or anything that BARDA needed.
    • About two hours later, Dr. Kadlec and Mr. Shuy called Dr. Bright. They told him that his presentation to Senator Blunt must have been phenomenal. In describing his impression of the briefing, Dr. Kadlec asked Dr. Bright if he was familiar with the phrase “catastrophic success.” Dr. Kadlec then told Dr. Bright that he had “good news” and “other news.” Dr. Kadlec’s good news was that Congress apparently had so much confidence in Dr. Bright that it was planning to give BARDA billions of dollars of additional funding, possibly in excess of $2 billion just to focus on diagnostics. According to Dr. Kadlec, Congress strongly believed in Dr. Bright and his ability to lead BARDA in combating COVID-19. Dr. Kadlec and Mr. Shuy were both extremely congratulatory, reiterating that Dr. Bright must have had a fantastic briefing with Senator Blunt.
    • Then, in order to create a pretext for Dr. Bright’s removal as BARDA Director, Dr. Kadlec fabricated a false narrative. Dr. Kadlec presented what he called his “other news.” He told Dr. Bright that Congress wanted BARDA and NIH to use the additional funding to work together on a special project focusing on diagnostics. Dr. Kadlec and Mr. Shuy then both disparaged NIH Director Francis Collins, calling him profane names and lamenting that Dr. Bright would have to “find a way” to collaborate with him on this project. According to Dr. Kadlec, Dr. Collins was trying to make political moves to take over some of BARDA’s territory and assume primary responsibility for vaccine development. Dr. Kadlec instructed Dr. Bright that he was to “get the money and write the checks” while “controlling Dr. Collins.” Before ending the call, Dr. Kadlec told Dr. Bright that this additional funding was going to make Dr. Bright “famous.” Dr. Bright found the comments and friendly attitude confounding, particularly given Dr. Kadlec’s hostile behavior towards him for months, if not years, as they repeatedly clashed on important issues.
    • That evening, Dr. Collins emailed Dr. Bright: “I’d like the chance to talk with you about closer collaboration between NIH and BARDA on COVID-19.” See email from F. Collins to R. Bright (Apr. 17, 2020), attached hereto as Exhibit 61. They made plans to talk in the morning and Dr. Bright worked through the night to prepare for the call. Believing that BARDA and NIH would be collaborating to develop diagnostics at the direction of Congress, Dr. Bright wanted to be prepared to discuss a high-level plan so that they could get started as soon as possible on this special project. That night, Dr. Bright called industry colleagues to discuss the issue and he outlined a strategy. The next morning, Dr. Bright called Dr. Kadlec to discuss the ideas he was planning to propose to Dr. Collins. Dr. Kadlec told Dr. Bright that his ideas were brilliant.
    • Unfortunately, Dr. Bright’s call with Dr. Collins did not go as planned. Dr. Collins began the call by telling Dr. Bright that he was going to become one of Dr. Collins’s deputies at NIH, and then began berating him. He said something to the effect of, “We’re going to be working closely, and I just want to be clear with you about a few things.” He then proceeded to tell Dr. Bright that Dr. Kadlec, Secretary Azar, and Congress all hated him, so according to Dr. Collins, he was doing Dr. Bright a favor by letting him come to NIH. Dr. Bright responded that he had just recently received a call from Dr. Kadlec saying Congress had such confidence in him and his organization that it was going to give BARDA billions of additional dollars. Dr. Bright concluded, “So your comments confuse me, but I probably need to take this back to my boss to talk about it.”
    • Dr. Bright then suggested that he and Dr. Collins discuss how to develop diagnostics to test people for COVID-19 and get Americans back to work. Dr. Bright shared his ideas, and Dr. Collins reacted positively. He said something to the effect of, “That sounds good, but I don’t understand why you don’t think you’re going to report to me like your boss said.” Dr. Bright said he would talk to Dr. Kadlec to clarify his role. After the call, Dr. Bright immediately called Dr. Kadlec and relayed what Dr. Collins said. Dr. Kadlec responded by calling Dr. Collins a “jackass” and insisting that he was “full of shit.” He said that Dr. Bright would get the money from Congress and would run the show. The call concluded with Dr. Kadlec’s assurances that he would “take care of” the confusion about Dr. Bright’s reporting structure.
    • Later that day, Dr. Bright received a frantic call from his Special Assistant, Gretta Blatner. She told Dr. Bright that the BARDA communications team had just informed her that they had taken Dr. Bright’s name and image off the ASPR website. According to the communications team, Dr. Bright had accepted a new job at NIH. Dr. Bright called Dr. Kadlec, but he did not answer. Dr. Bright sent him a text message saying that he was removed from the website because someone said he was moving to NIH. Dr. Kadlec responded in one word, all capitalized: “WHAT?” He said nothing else, and he did not return Dr. Bright’s call. About 10:00 p.m. that night, Dr. Bright received a call from ASPR Director of Communications Gretchen Michael who “congratulated” Dr. Bright for being an ASPR employee again. She told him that she had been instructed to restore Dr. Bright’s name and image to the website. In an effort to determine who had given the directions to remove, then restore Dr. Bright to ASPR’s website, Ms. Blatner made some phone calls at Dr. Bright’s direction. She soon learned that both directives came from Nikki Bratcher-Bowman, ASPR Director of Executive Management, who works for and reports only to Dr. Kadlec.
    • On Sunday, April 19, 2020, Dr. Bright conducted BARDA business as usual. While Dr. Collins told Dr. Bright that he was to report to him, Dr. Bright genuinely believed that Dr. Collins must have been mistaken. Even Dr. Kadlec had indicated that Dr. Collins was mistaken. Dr. Bright had no desire to work at NIH, and neither Dr. Kadlec nor anyone else had asked Dr. Bright if he wanted to transfer to NIH. Dr. Bright believed the website snafu must have been a misunderstanding, as well, especially because it was corrected within a day. That evening, Dr. Collins requested a phone call with Dr. Bright and they agreed to a call at 10:00 am the following morning.
    • Dr. Collins emailed Dr. Bright Monday morning before their call noting, “I don’t think we’re starting off on the right foot.” He told Dr. Bright that he had spoken to Dr. Kadlec, and the two agreed that Dr. Bright was to be a senior advisor to Dr. Collins at NIH, and no longer an employee at BARDA. He further explained that Dr. Disbrow would become BARDA’s Acting Director. Dr. Bright was stunned, and called Dr. Kadlec to relay what Dr. Collins had said in his email. Dr. Kadlec reiterated that Dr. Collins was a “jackass.” Dr. Bright asked if what Dr. Collins said was true, and Dr. Kadlec dodged the question and told Dr. Bright that he was going to have to work “really closely” with Dr. Collins. Dr. Bright asked if that meant he was being taken out of BARDA. Dr. Kadlec evaded again and said he would “look into it.” Immediately after this call, between 9:30 and 10:00 am that morning, Dr. Bright discovered that his email had been cut off.
    • Dr. Bright was late to his 10:00 am call with Dr. Collins. He told Dr. Collins that his email had been cut off and he was unable to access the videoconference portal, but he called in using a phone number that his Special Assistant was able to access from her email. Dr. Bright then explained that he was not trying to be difficult, but he remained confused because what Dr. Collins wrote in his email did not align with what Dr. Kadlec had just told him. Dr. Collins replied that he had talked that morning to Dr. Kadlec and the HHS Deputy Chief of Staff for Policy Paul Mango, who implements Secretary Azar’s policy, and both had communicated that the plan was for Dr. Bright to transfer to NIH. Dr. Collins then said something to the effect of: “I believe you’re being victimized here, you’re caught in the crosshairs. I didn’t see the need to move you out either.” At Dr. Collins’s suggestion, they ended the call so they could clear up any misunderstanding.
    • Shortly thereafter, Dr. Bright received a text message from Dr. Kadlec: “I’ve confirmed you’ve been assigned to NIH.” Dr. Bright immediately called Dr. Kadlec, but once again he did not answer. Throughout the rest of the day. Dr. Bright repeatedly called both Dr. Kadlec and, in an attempt to reach Dr. Kadlec, Ms. Bratcher-Bowman. Neither of them answered his calls. Later that day, Dr. Bright read media reports that he had been transferred to a more limited position at NIH. On April 21, 2020, HHS released a statement to the media confirming Dr. Bright’s ouster as Director of BARDA. HHS’s initial message was that Dr. Bright’s transfer from BARDA was “part of a bold plan to accelerate the development and deployment of novel point-of-care testing platforms.” [31 Nathaniel Weixel, Director of Agency Behind Vaccine Development Leaves Role, THE HILL (Apr. 21, 2020), https://thehill.com/policy/healthcare/493978-director-of-federal-agency-to-leadcoronavirus-vaccine-development-departs.] HHS also said that Dr. Bright would be tapped to lead a new “shark tank” effort to develop a COVID-19 test.  [32 Jeremy Diamond, Bright's Ouster Shines Light on Months of HHS Turmoil, CNN (Apr. 23, 2020), available at https://www.cnn.com/2020/04/23/politics/rick-bright-health-and-human-servicescoronavirus/ index.html.]
    • On April 22, 2020, Dr. Bright and his counsel released a statement objecting to his removal as Deputy Assistant Secretary for Preparedness and Response and Director of BARDA and his involuntary transfer to a more limited and less impactful position at NIH. He stated: “I believe this transfer was in response to my insistence that the government invest the billions of dollars allocated by Congress to address the COVID-19 pandemic into safe and scientifically vetted solutions, and not in drugs, vaccines and other technologies that lack scientific merit. I am speaking out because to combat this deadly virus, science – not politics or cronyism – has to lead the way.” Dr. Bright stated that he intended to file a whistleblower complaint with the Office of Special Counsel.
    • In response, HHS Leadership engaged in a baseless smear campaign against Dr. Bright, asserting, for the first time, that Dr. Bright was removed from his position for poor performance. This rationale is baseless and is undercut entirely by the stellar performance appraisals Dr. Bright was given by Dr. Kadlec. Dr. Bright had also recently received a significant monetary performance bonus in December and was appointed the MCM Czar by Dr. Kadlec when the COVID-19 response was shifted from HHS leadership to FEMA in March. This claim also defies the confidence shown in Dr. Bright and his leadership of BARDA as evidenced by Congress appropriating $3.5 billion directly to BARDA for the COVID-19 response. In another blatant act of retaliation, NIH Director Francis Collins announced on April 29, 2020, that Dr. Bright would not lead the new “shark tank” effort to develop a COVID-19 test and that his precise role “is under development.” Dr. Bright has not been assigned any responsibilities and duties and remains in limbo. As of April 20, 2020, he stopped receiving a paycheck.

IV. HHS’s involuntary transfer of Dr. Right violated the Whistleblower Protection Act.

• [Full complaint available at Dr. Rick Arthur Bright (born 1966)  ] 

The fast-growing list of possible treatments for the novel coronavirus includes an unlikely candidate: famotidine, the active compound in the over-the-counter heartburn drug Pepcid. On 7 April, the first COVID-19 patients at Northwell Health in the New York City area began to receive famotidine intravenously, at nine times the heartburn dose. Unlike other drugs the 23-hospital system is testing, including Regeneron’s sarilumab and Gilead Sciences’s remdesivir, Northwell kept the famotidine study under wraps to secure a research stockpile before other hospitals, or even the federal government, started to buy it. “If we talked about this to the wrong people or too soon, the drug supply would be gone,” says Kevin Tracey, a former neurosurgeon in charge of the hospital system’s research.

As of Saturday, 187 COVID-19 patients in critical status, including many on ventilators, have been enrolled in the trial, which aims for a total of 1174 people. Reports from China and molecular modeling results suggest the drug, which seems to bind to a key enzyme in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could make a difference. But the hype surrounding hydroxychloroquine and chloroquine—the unproven antimalarial drugs touted by President Donald Trump and some physicians and scientists—has made Tracey wary of sparking premature enthusiasm. He is tight-lipped about famotidine’s prospects, at least until interim results from the first 391 patients are in. “If it does work, we’ll know in a few weeks,” he says.

A globe-trotting infectious disease doctor named [Dr. Michael Vincent Callahan (born 1962)] was the first to call attention to the drug in the United States. Callahan, who is based at Massachusetts General Hospital and has extensive connections in the biodefense world, has spent time in disease hot zones around the world, including the 2003 outbreak of another coronavirus disease, SARS, in Hong Kong. In mid-January, he was in Nanjing, China, working on an avian flu project. As the COVID-19 epidemic began to explode in Wuhan, he followed his Chinese colleagues to the increasingly desperate city.

The virus was killing as many as one out of five patients older than 80. Patients of all ages with hypertension and chronic obstructive pulmonary disease were faring poorly. Callahan and his Chinese colleagues got curious about why many of the survivors tended to be poor. “Why are these elderly peasants not dying?” he asks.

In reviewing 6212 COVID-19 patient records, the doctors noticed that many survivors had been suffering from chronic heartburn and were on famotidine rather than more-expensive omeprazole (Prilosec), the medicine of choice both in the United States and among wealthier Chinese. Hospitalized COVID-19 patients on famotidine appeared to be dying at a rate of about 14% compared with 27% for those not on the drug, although the analysis was crude and the result was not statistically significant.

But that was enough for Callahan to pursue the issue back home. After returning from Wuhan [(when did he return?)], he briefed [Robert Peter Kadlec (born 1957)], assistant secretary for preparedness and response at the Department of Health and Human Services, then checked in with [Dr. Robert Wallace Malone (born 1959)], chief medical officer of Florida-based Alchem Laboratories, a contract manufacturing organization. Malone is part of a classified project called [DOMANE  ( "Discovery of Medical Countermeasures Against Novel Entities" , created by the Defense Threat Reduction Agency  in Dec of 2019 )] that uses computer simulations, artificial intelligence, and other methods to rapidly identify U.S. Food and Drug Administration (FDA)-approved drugs and other safe compounds that can be repurposed against threats such as new viruses.

[Dr. Robert Wallace Malone (born 1959)] had his eyes on a viral enzyme called the papainlike protease, which helps the pathogen replicate. To see whether famotidine binds to the protein, he would ordinarily need the enzyme’s 3D structure, but that would not be available for months. So Malone recruited computational chemist [Dr. Joshua Pottel (born 1989)], president of Montreal-based Molecular Forecaster, to predict it from two crystal structures of the protease from the 2003 SARS coronavirus, combined with the new coronavirus’ RNA sequence.

It was hardly plug-and-play. Among other things, they compared the gene sequences of the new and old proteases to rule out crucial differences in structure. [Dr. Joshua Pottel (born 1989)] then tested how 2600 different compounds interact with the new protease. The modeling yielded several dozen promising hits that pharmaceutical chemists and other experts narrowed to three. Famotidine was one. (The compound has not popped up in in vitro screens of existing drug libraries for antiviral activity, however.)

“If it does work, we’ll know in a few weeks,” says Northwell Health’s Kevin Tracey, who leads the famotidine study,

With both the tantalizing Chinese data and the modeling pointing toward famotidine, a low-cost, generally safe drug, Callahan contacted Tracey about running a double-blind randomized study. COVID-19 patients with decreased kidney function would be excluded because high doses of famotidine can cause heart problems in them.

After getting FDA approval, Northwell used its own funds to launch the effort. Just getting half of the needed famotidine in sterile vials took weeks, because the injectable version is not widely used. On 14 April, the U.S. Biomedical Advanced Research and Development Authority (BARDA), which operates under Kadlec, gave Alchem a $20.7 million contract for the trial, most of which paid Northwell’s costs.

The study’s draft protocol was aimed only at evaluating famotidine’s efficacy, but Trump’s “game-changer” antimalarial drug was rapidly becoming the standard of care for hospitalized COVID-19 patients. That meant investigators would only be able to recruit enough subjects for a trial that tested a combination of famotidine and hydroxychloroquine. Those patients would be compared with a hydroxychloroquine-only arm and a historic control arm made up of hundreds of patients treated earlier in the outbreak. “Is it good science? No,” Tracey says. “It’s the real world.”

Anecdotal evidence has encouraged the Northwell researchers. After speaking to Tracey, David Tuveson, director of the Cold Spring Harbor Laboratory Cancer Center, recommended famotidine to his 44-year-old sister, an engineer with New York City hospitals. She had tested positive for COVID-19 and developed a fever. Her lips became dark blue from hypoxia. She took her first megadose of oral famotidine on 28 March. The next morning, her fever broke and her oxygen saturation returned to a normal range. Five sick co-workers, including three with confirmed COVID-19, also showed dramatic improvements after taking over-the-counter versions of the drug, according a spreadsheet of case histories Tuveson shared with Science. Many COVID-19 patients recover with simple symptom-relieving medications, but Tuveson credits the heartburn drug. “I would say that was a penicillin effect,” he says.

After an email chain about Tuveson’s experience spread widely among doctors, Timothy Wang, head of gastroenterology at Columbia University Medical Center, saw more hints of famotidine’s promise in his own retrospective review of records from 1620 hospitalized COVID-19 patients. Last week, he shared the results with Tracey and Callahan, and he added them as a co-authors on a paper now under review at the Annals of Internal Medicine. All three researchers emphasize, though, that the real test is the trial now underway. “We still don’t know if it will work or not,” Tracey says.

Callahan has kept busy since his return from China. Kadlec deployed him on medical evacuation missions of Americans on two heavily infected cruise ships. Now back to doing patient rounds in Boston, he says the famotidine lead underscores the importance of science diplomacy in the face of an infectious disease that knows no borders. When it comes to experience with COVID-19, he says, “No amount of smart people at the [National Institutes of Health] or Harvard or Stanford can outclass an average doctor in Wuhan.”

Modest results from a federal trial of an experimental drug helped send the stock market soaring on Wednesday, another sign of the desperation for a viable treatment against the coronavirus.

Just before markets opened, Gilead, maker of the antiviral drug remdesivir, announced that it was “aware of positive data” about the drug’s performance in a federal trial, sending futures upward. Trading in the company’s shares was briefly halted.

Later, in a briefing at the White House, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said the trial had shown that treatment with the drug could modestly speed recovery in patients infected with the coronavirus.

The improvement in recovery times “doesn’t seem like a knockout 100 percent,” Dr. Fauci conceded, but “it is a very important proof of concept, because what it has proven is that a drug can block this virus.”

Sitting at Dr. Fauci’s side, President Trump said, “Certainly it’s positive, it’s a very positive event.” In past weeks, he has repeatedly hailed remdesivir as a potential “game changer,” despite spotty evidence.

Business leaders, scientists and politicians alike are scrambling to find ways to fight an insidious epidemic and to reopen a devastated economy. The virus has claimed at least 60,000 lives in the United States, and more than 200,000 worldwide. There have been precious few reasons for optimism, and the markets seized on the news.

The trial sponsored by the National Institute of Allergy and Infectious Diseases enrolled 1,063 patients who were given remdesivir or a placebo. The time to recovery averaged 11 days among those who got the drug, compared with 15 days for those who got the placebo.

There were fewer deaths in the remdesivir group, but the result did not reach statistical significance, Dr. Fauci said. Deaths were not a primary measure in the trial.

Dr. Fauci cautioned that the results of the study still needed to be properly peer-reviewed, but he was optimistic that remdesivir would become “the standard of care” for patients with Covid-19.

Some scientists were unsettled by the way in which the findings were reported. The disclosure of trial results in a political setting, before peer review or publication, is very unusual, said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic who has conducted dozens of clinical trials.

“Where are the data?” he asked. Scientists will need to see figures on harms associated with the drug in order to assess its benefits, he added.

“This is too important to be handled in such a sloppy fashion,” Dr. Nissen said.

Dr. Michele Barry, a global health expert at Stanford University, said she had faith in Dr. Fauci’s assessment. Still, she added, “It is unusual to call a drug the ‘standard of care’ until peer review of data and publication, and before studies have shown benefit in mortality.”

The Food and Drug Administration is likely at some point to announce an emergency approval for remdesivir, a senior administration official told The New York Times. Another drug touted by the president, hydrochloroquine, also was granted such an approval, but results in patients have been disappointing.

In one study of veterans with Covid-19, those receiving hydrochloroquine and an antibiotic died at higher rates than those given ordinary supportive care.

Mr. Trump also hopes to put in place a crash program to develop a vaccine, an undertaking being seen with skepticism even inside the administration. The accelerated process, known internally as Operation Warp Speed, would aim to produce hundreds of millions of doses by the end of this year.

But medical experts, including Dr. Fauci, have warned that developing a vaccine will require a year to 18 months at the earliest, and that rushing the process could endanger public health.

For now, drug treatment seems a more attainable goal.

“Remdesivir is not a magic bullet, but it’s as good as we get right now,” said Dr. Peter Chin-Hong, an infectious disease specialist at the University of California, San Francisco, and one of the trial’s investigators.  “Patients come to the hospital thinking we have a treatment, and by treatment, they mean a drug. [...] We have been impotent in not having any options.”

Remdesivir has never been approved as a treatment for any disease. It was developed to fight Ebola, but results from a clinical trial in Africa were disappointing.

But as the coronavirus pandemic took hold, the drug emerged as one of the more promising potential treatments. It interrupts the production of the virus in lab studies and seems safe in animals.

Until now, high expectations for remdesivir have been fueled largely by anecdotal reports of Covid-19 patients who took the drug and recovered.

Two such reports were published in the prestigious New England Journal of Medicine, lending credibility to what researchers said were actually uncertain results.

Without trials comparing the drug to a placebo, it has been impossible to know whether the drug made a difference or patients got better on their own with normal supportive care.

A separate study of remdesivir, published on Wednesday in The Lancet, found no benefit to the drug, compared with placebo.

“Unfortunately, our trial found that while safe and adequately tolerated, remdesivir did not provide significant benefits over placebo,” said the lead investigator of the new study, Dr. Bin Cao of the China-Japan Friendship Hospital and Capital Medical University in Beijing.  [He added, ] “This is not the outcome we hoped for.”

The results are hard to interpret, because the study was far smaller than planned — enrolling 236 patients instead of the 453 that had been expected, because there were too few severely ill patients now in China.

Dr. Eric Peterson, a clinical trials expert at Duke University, said that with too few patients, “all you can say is it doesn’t seem to work in this population.” If there had been a big effect of the drug, he added, that would have been seen.

He added that the trial should not be repeated with this population, but instead in those who are less severely ill.

“This is a flawed study,” Dr. Barry said, but results might improve if the drug were given at a higher dose or earlier in the course of the disease.

Acceding to demands, Gilead has distributed the drug to hundreds of patients under so-called compassionate use, a regulatory exemption by which patients may receive a drug apart from a clinical trial.

Gilead itself published reports of uncontrolled studies. On Wednesday, in another news release, the company announced that a study comparing a five- to 10-day course of treatment with the drug showed that those getting the shorter course of treatment did just as well.

That study had no control group and was “noninformative,” Dr. Peterson said.

CHICAGO (Reuters) - Concerns over leaks compelled the top U.S. infectious disease official to reveal data on Gilead Sciences Inc’s experimental drug remdesivir, the first in a scientifically rigorous clinical trial to show benefit in treating COVID-19.

The dramatic announcement by Dr Anthony Fauci in the Oval Office on Wednesday prompted concerns among scientists that the Trump administration was raising hopes about a coronavirus treatment before sharing the full data with researchers.

As a cautionary example of inflating the potential value of a therapy, some pointed to President Donald Trump’s repeated endorsements of malaria drug hydroxychloroquine as a treatment, with no evidence that it works.

Newer data suggests the malaria treatments may carry significant risks for some sufferers of the respiratory disease caused by the virus.

Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), which is running the trial, said he took the first opportunity to get the word out that patients taking a dummy treatment or placebo should be switched to remdesivir in hopes of benefiting from it.

He expressed concern that leaks of partial information would lead to confusion. Since the White House was not planning a daily virus briefing, Fauci said he was invited to release the news at a news conference with Louisiana Gov. John Bel Edwards(D). “It was purely driven by ethical concerns,” Fauci told Reuters in a telephone interview.

“I would love to wait to present it at a scientific meeting, but it’s just not in the cards when you have a situation where the ethical concern about getting the drug to people on placebo dominates the conversation.”

An independent data safety and monitoring board, which had looked at the preliminary results of the NIAID trial, determined it had met its primary goal of reducing hospital stays.

On Tuesday evening, that information was conveyed in a conference call to scientists studying the drug globally.

“There are literally dozens and dozens of investigators around the world,” Fauci said. “People were starting to leak it.” But he did not give details of where the unreported data was being shared.

Several scientists interviewed by Reuters felt the White House setting seemed inappropriate for the release of highly anticipated government-funded trial data on the Gilead therapy.

They had expected it to be presented simultaneously in a detailed news release, a briefing at a medical meeting or in a scientific journal, allowing researchers to review the data.

Information from various trials of remdesivir has been leaked to media in recent weeks. In a statement on Wednesday, Gilead said the NIAID’s much anticipated trial had met its primary goal, but gave no details.

Data in a separate NIAID statement after Fauci spoke detailed preliminary results showing that patients who got the drug had a 31 percent faster time to recovery than those who got a placebo, cutting hospital stays by four days.

The trial also came close to showing the drug helped people survive the disease, but the data fell just short of statistical significance.

“I want to see the full data. I want to understand the statistics. I want to understand the benefit and risk. I want to understand the structure of the study, and all of it,” said Dr. Steven Nissen, the chief academic officer at the Cleveland Clinic.

“Am I encouraged from what I’ve heard? Yes, I’m encouraged. But I want to get a full understanding of what happened here, and not get it via a photo opportunity from the Oval Office.”

Data Gilead released on its own trial of remdesivir drew less attention, as it did not compare outcomes between those receiving therapy and those who did not.

Results from a third study in China suggesting remdesivir failed to help COVID-19 patients were released in the British medical journal the Lancet after review by a peer group of scientists.

“That’s the only thing I’ll hang my hat on, and that was negative,” said Dr. Eric Topol, director and founder of the Scripps Research Translational Institute in La Jolla, California.

He was unimpressed by remdesivir’s modest benefit.

“It was expected to be a whopping effect,” Topol added. “It clearly does not have that.”

At the Oval Office news conference, Fauci compared the study findings to AZT, the first drug to show any benefit against HIV, decades ago.

“We know that was an imperfect drug. It was the first step,” Fauci said in the interview. “Similar to AZT, it’s (remdesivir) the first baby step towards what hopefully will be a number of better drugs that will come in and be able to treat people with COVID-19.”

Government clinical trial investigators changed the primary metric for measuring the success of Gilead’s experimental drug remdesivir as a coronavirus treatment two weeks before Anthony S. Fauci’s announcement that the drug would be the new “standard of care.” 

Instead of counting how many people taking the drug were kept alive on ventilators or died, among other measures, the National Institute of Allergy and Infectious Diseases said it would judge the drug primarily on a different outcome: how long it took surviving patients to recover. 

Death and other negative outcomes were moved to secondary measure status: They would still be tracked, but they would no longer be the key measure of remdesivir’s performance. The switch — which specialists said is unusual in major clinical trials but not unheard of — was publicly disclosed on the government’s clinicaltrials.gov website on April 16 but did not receive much attention at the time.

The change reflects evolving scientific understanding of the fast-moving nature of the virus and uncertainties around how the lethal effects reveal themselves in patients, said NIAID, Gilead, and outside specialists. But the change also adds weight to the assessment of government and medical researchers that remdesivir is not a knockout drug that will change the trajectory of the coronavirus pandemic.

On Friday, as expected, the Food and Drug Administration approved an emergency use authorization for the drug that will allow it to be prescribed for hospitalized patients infected with the coronavirus.

The newly adopted criteria were a central feature of this week’s declaration by Fauci, NIAID’s director, that remdesivir reduced the time to recovery for surviving patients from 15 days to 11 days, a 31 percent improvement.

“The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery,'' Fauci said as he sat in an Oval Office meeting with President Trump and other members of the president’s coronavirus task force. “It’s highly significant.''

The difference in death rate, one of the original primary measures, was not statistically significant, Fauci said, showing only a marginal reduction from 11 percent in patients given a placebo to 8 percent in patients given remdesivir. Full release of the trial results would be made soon, Fauci said.

Some medical research specialists questioned the change in the primary outcome measure of the trial, which had 1,063 patients.

“I think that they thought they weren’t going to win, and they wanted to change it to something they could win on,'' said Steven Nissen, a Cleveland Clinic cardiologist and expert clinical investigator who has led numerous drug trials. “I prefer the original outcome. It’s harder. It’s a more meaningful endpoint.

“Getting out of the hospital early is useful,'' he said, “but it’s not a game-changer.'' 

Nissen expressed dismay that the placebo phase of the trial was declared over so quickly, when a few more weeks might have provided a pool of patients large enough to show a statistically beneficial difference in death. 

But Fauci said Wednesday that ethical considerations drove the announcement: As soon as a clear evidence of shorter hospitalizations was available, trial investigators owed it to patients on placebo to stop that phase of the trial so they could access the drug. 

When the trial began on Feb. 21, it was designed to focus on collecting eight patient outcomes, to be measured on the 15th day after treatment. The list of outcomes was similar to guidance the World Health Organization issued in February for coronavirus clinical trials. 

The original NIAID trial list started with death, followed by five categories of hospitalized patients: on ventilator or ECMO machine (which oxygenates blood outside the body); on high-flow oxygen therapy; on basic supplemental oxygen; not requiring oxygen but requiring ongoing care; not requiring care. The final two categories covered patients released from the hospital.

NIAID said in response to questions Thursday that it made the switch eight weeks later to the more limited measure of “time to recovery'' based on modeling that took into account new information about the course of the disease. The initial measurement period of two weeks, it said, was deemed to be too short as scientists learned more about the lengthy time patients could be seriously ill with covid-19, NIAID said.

“Little was known regarding the natural course of covid-19 when the trial was initially designed, and the initial endpoint chosen specified a single timepoint for evaluation, namely day 14,” the institute said. “However, with the growing knowledge during the epidemic, we learned that covid-19 had a more protracted course than previously known.

“NIAID statisticians performed modeling of what happens if the right day is not picked for assessment, which revealed that meaningful treatment effects could be missed with that primary endpoint,'' NIAID said. “Time to recovery avoids this issue, and the change in primary endpoint seemed appropriate given the evolving clinical data.''

Government researchers who decided to make the switch in outcome measure did not have access to clinical data, NIAID added.

Gilead did not respond to a question about whether it had input on the decision to change the endpoint.

“NIAID changed the primary endpoint while the study was blinded,'' Gilead spokesman Ryan McKeel said in an email, a decision he said was “based on continuing discussions and evolving understanding of the disease.'' He added that it is important to note that death, ventilation and other measures are included in the list of the trial’s secondary outcome measures “and will be reported when the data are published."

An exact timetable for publication of the results has not been disclosed. In the absence of any other treatment for coronavirus, Fauci declared that remdesivir would become the standard of care for certain hospitalized patients. Clinicians are eagerly awaiting more data from the trial so they will know which patients stand to benefit the most.

Fauci’s announcement coincided with more negative results for remdesivir published in the medical journal The Lancet; that trial, a Chinese study that was stopped early because it did not recruit enough patients, showed no benefit of remdesivir over placebo, and also no benefit in survival.

Some experts in clinical trials raised questions about the change in outcome measures.

“It raises a lot of flags, and it requires a lot of answers,” Walid F. Gellad, a professor of health policy and management at the University of Pittsburgh’s Department of Medicine, said in an interview, “especially when people start saying it’s become the standard of care, and all we saw was a news release in a trial with an outcome that was changed two weeks ago. It really is striking.''

An expert in transparency in clinical trials at the University of Oxford, Henry Drysdale, said the Oval Office setting of Fauci’s announcement, combined with the limited data disclosed, raised important questions about the outcomes change that will need to be answered when the full results are published in a peer-reviewed journal. Drysdale is part of a team of researchers who, in a landmark study published last year, found discrepancies in trial designs and reported outcomes in major academic journals.

“It’s extremely worrying that those very important outcomes were dropped from the primary outcome,'' Drysdale said in an interview. Asked to assess NIAID’s statement issued to reporters on Thursday, Drysdale said, “Whenever I see an explanation like this, when an outcome-switching has happened, that’s fine, but you were not open about this when you reported your quote-unquote exciting results."

But a strong degree of transparency about the change, combined with NIAID’s assurances that trial leaders did not know trial results when they switched the outcome, should settle any lingering questions, experts agreed.

Milton Packer, a cardiologist and clinical trial investigator at Baylor University Medical Center, said that, based on Fauci’s disclosures, roughly 95 people died in both arms of the trial. That combined number may have led investigators to believe they would not have a large enough sample of deaths to be statistically significant, he said.

“If you knew that the number of observations was inadequate to answer the question, and you did not know the breakdown, then shifting the endpoint is not a problem,” Packer said.

Until last weekend, treatment for COVID-19 was primarily experimental. In hundreds of clinical trials across the globe, researchers are testing new drugs, as well as those that scientists created for other purposes, to stem the death toll the world is facing.

On March 28, 2020, the FDA [ https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#covidtherapeutics ]   gave permission to doctors to use hydroxychloroquine sulfate and chloroquine phosphate products for the treatment of COVID-19 in adolescents and adults in situations where clinical trials were not an option. 

Despite the hype around these drugs, the FDA followed up with an announcement on April 24, 2020, to highlight that they were investigating reports that some people had developed serious heart rhythm problems in response to the drugs. 

“Hydroxychloroquine and chloroquine have not been shown to be safe and effective for treating or preventing COVID-19. They are being studied in clinical trials for COVID-19, and we authorized their temporary use during the COVID-19 pandemic for treatment of the virus in hospitalized patients when clinical trials are not available, or participation is not feasible, through an [EUA],” the FDA statement [ https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or ] reads. 

Much attention has since focused on a drug called remdesivir.

APPROVED FOR COVID-19

Veklury (remdesivir) is the first drug approved [ https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19 ]  by the Food and Drug Administration (FDA) to treat COVID-19, the disease caused by the new coronavirus. Veklury is approved to treat diagnosed or suspected COVID-19 in certain hospitalized people. The drug was previously granted an Emergency Use Authorization (EUA) [ https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization ] by the FDA. This article is currently being updated to reflect this change.

What is remdesivir?

Pharmaceutical company Gilead Sciences, Inc. developed remdesivir as part of their antiviral drug portfolio to treat viral infections. This included work on coronaviruses. 

Back in 2017, a team of researchers from the University of North Carolina at Chapel Hill and Vanderbilt University in Nashville, TN, published a study with Gilead in the journal Science Translational Medicine [ https://stm.sciencemag.org/content/9/396/eaal3653?utm_campaign=toc_stm_2017-06-28&et_rid=17050501&et_cid=1410533 ] about remdesivir and coronaviruses. 

“This drug was effective against multiple types of coronaviruses in cell culture[s] and in a mouse model of SARS and did not seem to be toxic,” the authors wrote in their paper. “Given its broad activity, this antiviral could be deployed to prevent spreading of a future coronavirus outbreak, regardless of the specific virus that jumps over.”

Gilead and the National Institutes of Health (NIH) also tested the drug in clinical trials for the treatment of Ebola [ https://www.niaid.nih.gov/diseases-conditions/ebola-treatment ] , but they announced in August last year that two other drugs are more effective. 

So, how does remdesivir work?

The answer to this question became clearer earlier this year, when a team from the University of Alberta in Edmonton, Canada — along with scientists from Gilead — published a paper in the Journal of Biological Chemistry. 

Coronaviruses use an enzyme called RNA-dependent RNA polymerase to copy their genetic material when they replicate inside an infected cell. Remdesivir is a nucleotide analog, or a synthetic mimic of a naturally occurring molecule that viruses need for replication. 

According to the researchers, remdesivir stops the replication process in their model of the coronavirus that causes MERS.

Contradictory clinical studies

On February 25, 2020, the NIH [ https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins ] began enrolling people into their remdesivir clinical trial to test the drug’s safety and efficacy in the treatment of COVID-19. 

Several weeks earlier, researchers in China — along with international collaborators — started a separate trial of the drug in 10 hospitals in Hubei, China. 

On April 23, 2020, news of the study’s failure began to circulate. It seems that the World Health Organization (WHO) had posted a draft report about the trial on their clinical trials database, which indicated that the scientists terminated the study prematurely due to high levels of adverse side effects. 

The WHO withdrew the report, and the researchers published their results in The Lancet [ https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext ]  on April 29, 2020. 

The number of people who experienced adverse side effects was roughly similar between those receiving remdesivir and those receiving a placebo. In 18 participants, the researchers stopped the drug treatment due to adverse reactions.

What did the results say about the efficacy of the drug for treating COVID-19?

“Remdesivir use was not associated with a difference in time to clinical improvement,” write the authors in the paper. They did highlight that people who had symptoms that lasted 10 days or under did recover faster, although these results were not statistically significant.

One caveat with their study was the number of participants; the researchers terminated the trial earlier than planned as they were unable to recruit any more volunteers. 

“Our trial did not attain the predetermined sample size because the outbreak of COVID-19 was brought under control in China,” they explain. 

Studies indicate remdesivir’s benefits

However, also on April 29, 2020, the National Institute of Allergy and Infectious Diseases (NIAID) announced that their NIH trial showed that remdesivir treatment led to faster recovery in hospital patients with COVID-19, compared with placebo treatment. 

“Preliminary results indicate that patients who received remdesivir had a 31% faster time to recovery than those who received placebo,” according to the press release [ https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19 ]. “Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo.” 

The mortality rate in the remdesivir treatment group was 8%, compared with 11.6% in the placebo group, indicating that the drug could improve a person’s chances of survival. These data were close to achieving statistical significance. 

“More detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report,” the press release continues. 

To add to the story, on the same day, Gilead also issued a press statement about their phase III clinical trial of the drug. In the trial, the company compared 5 days of treatment with 10 days of treatment. There was no placebo group.

According to the company, 5 days of treatment had similar effects to 10 days of treatment in people with severe COVID-19. 

“These study results complement data from the placebo-controlled study of remdesivir conducted by the [NIAID] and help to determine the optimal duration of treatment with remdesivir,” says Chief Medical Officer Dr. Merdad Parsey. 

“The study demonstrates the potential for some patients to be treated with a 5-day regimen, which could significantly expand the number of patients who could be treated with our current supply of remdesivir. This is particularly important in the setting of a pandemic, to help hospitals and healthcare workers treat more patients in urgent need of care.”

The EUA

On May 1, 2020, the FDA gave the go-ahead for clinicians to use remdesivir outside of clinical trials to treat COVID-19 in certain people.

“Today, the [FDA] issued an [EUA] for the investigational antiviral drug remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease,” a press statement [ https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment ] reads. 

“While there is limited information known about the safety and effectiveness of using remdesivir to treat people in the hospital with COVID-19, the investigational drug was shown in a clinical trial to shorten the time to recovery in some patients.”

EUA [ https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#abouteuas ] is a type of approval that the FDA can issue for a medical product in situations that are serious or life threatening. 

Prof. Stephen Evans, from the London School of Hygiene & Tropical Medicine in the United Kingdom, elaborates on this type of approval: 

“The key element is that ‘there is no adequate, approved, and available alternative to the emergency use of remdesivir for the treatment of COVID-19.’ It sets out the conditions under which remdesivir may be distributed and used. It does not allow Gilead to market the drug. In this case, it allows doctors to obtain and use the drug in hospitalized patients with known or suspected severe COVID-19 and who require at least supplemental oxygen. The doses are set out and it must be injected in a hospital.”

Regarding whether or not the evidence available was sufficient to support the FDA’s decision to grant EUA, Prof. Evans explains that the study in The Lancet was well-conducted but ultimately too small to draw any conclusions. 

“While compatible with the results shown in the NIAID trial, taken together they show the evidence of efficacy may not be quite as great as shown in the NIAID trial on its own,” he says. “In addition, there is another Chinese trial, also stopped because the numbers of new patients with COVID-19 had fallen in China so they were unable to recruit, which has not yet published its data,” Prof. Evans continues. “There are other trials where remdesivir is compared with non-remdesivir treatments currently [being] done and results from some of these should appear soon. A wider view will give a better understanding of the benefits and harms with remdesivir, but in this emergency, it is not totally unreasonable of the FDA to allow for its use, but it would undoubtedly have been better to provide more of the evidence in public.”

Remdesivir’s modest effects

In a statement on April 29, 2020, Dr. Anthony Fauci, head of the NIAID, explained that the drug reduced the time that people were in the hospital by around 4 days — a 31% faster recovery time.  “Although a 31% improvement doesn’t seem like a knockout 100%, it is a very important proof of concept,” he says. “What it has proven is that a drug can block this virus.”

In an interview with Reuters, Dr. Fauci explained why he had chosen to announce the results of the organization’s clinical trial last week. 

“It was purely driven by ethical concerns,” he added. “I would love to wait to present it at a scientific meeting, but it’s just not in the cards when you have a situation where the ethical concern about getting the drug to people on placebo dominates the conversation.”

The reception by the scientific community has been mixed. 

“It was expected to be a whopping effect,” Dr. Eric Topol — director of the Scripps Research Translational Institute in La Jolla, California — told Reuters, expressing his disappointment at the drug’s modest improvements. “It clearly does not have that.”

Others criticized the fact that the NIAID did not release the full dataset from their study. 

“I want to see the full data. I want to understand the statistics. I want to understand the benefit and risk,” Dr. Steven Nissen, chief academic officer at the Cleveland Clinic, said to Reuters. “I want to understand the structure of the study, and all of it.” 

“Remdesivir is not a cure for COVID-19,” said Prof. Derek Hill, from University College London in the U.K. “There is evidence from the preliminary analysis that it speeds up patient recovery. When more data [are] available, this may tell us whether or not remdesivir can save lives as well as speed up recovery.”

Meanwhile, Dr. Fauci acknowledged that the drug was not a panacea and drew parallels to the early work around the drug AZT to treat HIV. 

“We know that was an imperfect drug. It was the first step,” he told Reuters. “Similar to AZT, it’s the first baby step toward what hopefully will be a number of better drugs that will come in and be able to treat people with COVID-19.”

Only time will tell how much remdesivir and any future iterations of the drug will change the course of the pandemic. Other clinical trials of the drug are ongoing, and our only option is to eagerly await the results and see how they compare with the research so far.

COVID-19 Drugs: A research study by Columbia University, Northwell Health and Massachusetts General Hospital shows that Famotidine, a common heartburn drug improved the clinical outcomes of hospitalized COVID-19 patients.

The study involving 1620 patients from more than 10 hospitals in the United States showed that Famotidine associated with reduced risk of intubation or death in hospitalized COVID-19 patients. However further randomized controlled trials are warranted and also detailed studies are needed to understand the mode of its efficacy. ( See  https://www.medrxiv.org/contenU10.1101 /2020.05.01 .20086694v1 .full.pdf+html ).

The drug was chosen as earlier drug repurposing computer modeling studies showed that the drug molecular structure had very good potential to block 'docking sites' on the spike protein structures of the SARS-CoV-2 coronavirus, rendering the virus to become inactive and not capable of entering host cells and replicating.

Famotidine is an approved US FDA drug has been on the market for nearly 40 years and is an active ingredient in the popular over-the-counter heartburn treatment Pepcid.

Dr Joseph Conigliaro, a coauthor of the research study and a doctor at Northwell Health said, "Based on what we've learned in this study, it's encouraging. This association is actually really compelling."

Of the 1,536 patients in the study who were not taking famotidine, 332, or 22%, either died or were intubated and put on a ventilator. Among the 84 patients who were taking famotidine, 8, or 10%, died or were put on a ventilator.

Dr Conigliaro added, "Compared to the rest of the patients, those who received famotidine had a greater than 2-fold decreased risk of either dying or being intubated."

Patients who were taking famotidine started the drug within 24 hours of being admitted to the hospital. Some took it orally and some intravenously, at varying dosages. About 15% of them were already taking it at home.

Medical researchers from Columbia University Irving Medical Center said, "It is not clear why those patients who received famotidine had improved outcomes. This is merely an association, and these findings should not be interpreted to mean that famotidine improves outcomes in patients hospitalized with COVID-19."

Doctors from other hospitals are warned not to prescribe famotidine just yet till the results of another clinical trial is concluded. This clinical trial, where patients are randomly assigned to get either famotidine or a placebo and then studied, can determine if the drug really works against COVID-19.

Columbia University and Northwell Health and are now conducting a clinical trial where some patients are receiving intravenous famotidine at a dosage nine times higher than what is given for heartburn. Others are receiving a placebo, or a drug that does nothing. Dr Conigliaro, who's heading up that trial, said preliminary results would likely be announced in a few weeks.

Dr Conigliaro said 233 patients have been enrolled in the study, and Northwell had planned to announce preliminary results when they enrolled 390 patients. However, since the number of patients with coronavirus in New York has declined, they might decide to announce the preliminary results with fewer patients.

A world renowned infectious disease doctor, Dr Michael Callahan from Massachusetts General Hospital was the first to call attention to the drug in the United States. In mid-January, he was in Nanjing, China, working on an avian flu project. As the COVID-19 epidemic began to explode in Wuhan, he followed his Chinese colleagues to the increasingly desperate city.

The virus was killing as many as one out of five patients older than 80. Patients of all ages with hypertension and chronic obstructive pulmonary disease were faring poorly. Dr Callahan and his Chinese colleagues got curious about why many of the survivors tended to be poor. In analyzing 6212 COVID-19 patient records, the physicians noticed that many survivors had been suffering from chronic heartburn and were on famotidine rather than more-expensive omeprazole (Prilosec), the medicine of choice both in the United States and among wealthier Chinese. Hospitalized COVID-19 patients on famotidine appeared to be dying at a rate of about 14% compared with 27% for those not on the drug.

Upon returning from Wuhan, he briefed Dr Robert Malone, chief medical officer of Florida-based Alchem Laboratories, a contract manufacturing organization. Dr Malone is part of a classified project called DO MANE that uses computer simulations, artificial intelligence, and other methods to rapidly identify U.S. Food and Drug Administration (FDA)approved drugs and other safe compounds that can be repurposed against threats such as new viruses.

Dr Malone had his eyes on a viral enzyme called the papain-like protease, which helps the pathogen replicate. To see whether famotidine binds to the protein, he needed the enzyme's 3D structure and recruited computational chemist Joshua Pottel, president of Montreal-based Molecular Forecaster, to create the modeling involving two crystal structures of the protease from the 2003 SARS coronavirus, combined with the new coronavirus' RNA sequence and to predict the drug molecular structure ability to 'dock' on those sites.

Among other things, they compared the gene sequences of the new and old proteases to rule out crucial differences in structure. Pottel then tested how 2600 different compounds interact with the new protease. The modeling yielded several dozen promising hits that pharmaceutical chemists and other researchers narrowed to three. Famotidine was one. (The compound has not popped up in in vitro screens of existing drug libraries for antiviral activity, however.)

Armed with he research from China and the modeling pointing toward famotidine, a low-cost, generally safe drug, Dr Callahan contacted Dr Kevin Tracey, a former neurosurgeon in charge of the Northwell hospital system's research about running a double-blind randomized study. COVID-19 patients with decreased kidney function would be excluded because high doses of famotidine can cause heart problems in them.

Upon securing the US FDA approval, Northwell used its own funds to launch the effort. Just getting half of the needed famotidine in sterile vials took weeks, because the injectable version is not widely used. On 14 April, the U.S. Biomedical Advanced Research and Development Authority (BARDA) gave Alchem a US$20.7 million contract for the trial, most of which paid Northwell's costs.

The anecdotal evidence had encouraged the Northwell researchers. After speaking to Dr Tracey, Dr David Tuveson, director of the Cold Spring Harbor Laboratory Cancer Center, recommended famotidine to his 44-year-old sister, an engineer with New York City hospitals. She had tested positive for COVID-19 and developed a fever. Her lips became dark blue from hypoxia. She took her first megadose of oral famotidine on 28 March. The next morning, her fever broke and her oxygen saturation returned to a normal range. Five sick co-workers, including three with confirmed COVID-19, also showed dramatic improvements after taking over-the-counter versions of the drug, according a spreadsheet of case histories Dr Tuveson shared.

After an email chain about Tuveson's experience spread widely among doctors, Dr Timothy Wang, head of gastroenterology at Columbia University Medical Center, saw more hints offamotidine's promise in his own

retrospective review of records from 1620 hospitalized COVID-19 patients. He shared the results with Dr Tracey and Dr Callahan, and he added them as a co-authors on a paper now under review at the Annals of Internal Medicine.

Some medical experts say that when analyzing study and clinical trial results of chloroquine, hydroxychloroquine and remdesivir, famotidine might be a better alternative compared to a toxic drug like remdesivir that is extremely expensive (ie between US$ 6,000 to US$12,000 per dose) and has yet to show any true efficacy against the SARS-CoV-2 coronavirus except for data that shows its shortens hospitalization. Despite lack of concrete efficacy proof and also safety studies of the drug, remdesivir is already being approved for usage by the US FDA to treat COVID-19.

Famotidine is a commonly used drug to treat gastric reflux and is also extremely cheap. In most Asian countries, a generic packet of 100 tablets of famotidine tablets cost less than US $3. A vial of 40mg injectable famotidine costs only US $4. In the study, both oral and intravenous versions were used. However Thailand Medical News warns readers to not to self-presecribe and to always consult a doctor before taking any drugs or supplements.

Doctors and scientists are studying many existing drugs with the hope of finding therapies they can repurpose to fight COVID-19. Some of these, like Gilead Sciences’ remdesivir, directly go after the virus SARS-CoV-2, which causes the disease. Others, like Incyte’s ruxolitinib, aim to dampen the overactive immune response that characterizes later stages of disease in COVID-19.

And then there are the oddballs. Take famotidine, the active ingredient in the over-the-counter heartburn drug Pepcid. The histamine-H2-receptor antagonist works by preventing stomach acid production. That it would have any activity in an infectious disease is a bit of a head-scratcher.

Doctors first became interested in famotidine after hearing reports that people in China who took the drug for heartburn were surviving COVID-19, while other people who essentially had the same risk factors but were taking different heartburn drugs like cimetidine or omeprazole (sold in the US as Tagamet and Prilosec, respectively) were dying from the disease. Perhaps famotidine was somehow bolstering these patients and improving their chances for survival.

In early April, doctors began a clinical trial at New York’s Northwell hospitals to test that theory. [See SARS-COV2 famotidine trials (2020)] They reasoned that even if evidence for famotidine’s effectiveness was largely anecdotal, the drug has been around since the 1980s and has a good safety profile. If it worked, it would be a fast and cheap way to ease the symptoms of COVID-19.

They decided to use high doses of intravenous famotidine. Their goal was to enroll 1,200 people with moderate to severe COVID-19 and see if those that got famotidine were less likely to die or require a ventilator. Then, in late April, the first news report about the trial appeared in Science. Boxes of Pepcid began to fly off of pharmacy shelves as people sought out any potential remedy during the pandemic.

Shortly afterward, on May 8, a team, led by Columbia University doctors Daniel Freedberg and Julian Abrams, posted a study on the preprint server medRxiv that compared the outcomes of people with COVID-19 who were prescribed famotidine within 24 hours of being admitted to the hospital to those who didn’t get the heartburn drug. They looked at the records of more than 1,600 patients at Columbia University Irving Medical Center between late February and mid-April. Of those, 84 patients received 10–40 mg of intravenous famotidine daily over the course of about 6 days.

The patients who got famotidine fared better. According to the study, they were far less likely to die or require a ventilator—a twofold decrease in risk—than those not receiving the drug. The results were published in the peer-reviewed journal Gastroenterology later in May (2020, DOI: 10.1053/j.gastro.2020.05.053).

“This is merely an association, and these findings should not be interpreted to mean that famotidine improves outcomes in patients hospitalized with COVID-19,” the team says in a statement. “It is also not clear why those patients who received famotidine had improved outcomes.”

For clarity on famotidine’s effectiveness, the team recommends awaiting the outcome of the trial going on at Northwell hospitals. “Hopefully the results from this trial will determine whether famotidine is efficacious for the treatment of COVID-19,” the team says in its statement.

Meanwhile, in early June, the journal Gut published a small case series of 10 people who developed COVID-19 and reported taking famotidine during their illness (2020, DOI: 10.1136/gutjnl-2020-321852). These people were not sick enough to go to the hospital, but their symptoms, such as cough and shortness of breath, improved within a day or two of taking the heartburn drug. It’s a small study, and the researchers acknowledge that it’s not enough to establish there’s any real benefit from taking famotidine for people who have COVID-19. Those authors recommend a clinical trial with famotidine be carried out with patients with milder disease in addition to the trial going on at Northwell hospitals.

Matthew D. Hall, acting director of biology and group leader, Early Translation Branch, at NIH’s National Center for Advancing Translational Sciences :    "I think there’s going to be some intriguing science trying to draw a connection between the activity—if it is proven to have that in patients—and how it’s actually working in the context of SARS-CoV-2 infection."

But the Northwell trial has slowed for two reasons, says Joseph Conigliaro, the physician who is leading it. Cases of COVID-19 in New York have declined, making it challenging to reach the enrollment requirements for the study.

And shifting treatment approaches have further complicated efforts. When the trial began, COVID-19 patients in New York were getting the antimalarial hydroxychloroquine as part of their treatment regimen. So the study was designed to compare patients receiving hydroxychloroquine and famotidine with patients receiving hydroxychloroquine and a placebo. But that standard treatment regimen has changed, and hydroxychloroquine is no longer given routinely. As a consequence, the researchers are looking to modify the study’s protocol, Conigliaro says.

Until the results of the study are in, Conigliaro can’t say whether famotidine works. “As a physician, I can’t tell people ‘go out and buy famotidine, and if you start getting an inkling of anything start taking it,’ ” he says. Even though the drug has long been considered safe, it’s unclear how to guide people to take it in terms of dose and disease stage. “We need to wait for the results of our trial,” he says.

Scientists are meanwhile trying to figure out why a heartburn medicine might also fight COVID-19. Using computational methods, a group in China used SARS-CoV-2 genes to predict the structures of viral proteins. The group then computationally screened existing drugs to see which could potentially act on those protein targets. Their study suggests that famotidine could inhibit the virus’s 3-chymotrypsin-like protease, which plays a role when the coronavirus makes copies of itself while inside the host (Acta Pharm. Sin. B 2020, DOI: 10.1016/j.apsb.2020.02.008).

Similarly, computational chemists at the scientific software company Molecular Forecaster virtually docked a library of 2,700 existing drugs and nutraceuticals to see which fit into a model of the papain-like protease, another key protein in SARS-CoV-2 replication. They were collaborating with scientists working for a US Department of Defense project called [DOMANE]. Famotidine was one of a few drugs that appeared to interact with the protease in the computational studies, says [Dr. Robert Wallace Malone (born 1959)], a physician and consultant who is on the [DOMANE] team.

But other evidence derails those computational studies. Matthew D. Hall, acting director of biology and group leader, Early Translation Branch, at the National Center for Advancing Translational Sciences (NCATS), part of the US National Institutes of Health, points out that his group did studies in cells that show famotidine doesn’t have any ability to fight SARS-CoV-2. “In a direct antiviral assay, we don’t see any activity for any of the compounds in this class,” he says.

As a drug-repurposing candidate, Hall says, famotidine is attractive because it’s safe, affordable, and accessible. But making further conclusions about its usefulness in COVID-19 will require clinical trial data. If those trials show promise, Hall says, “I think there’s going to be some intriguing science trying to draw a connection between [clinical] activity and how it’s actually working in the context of SARS-CoV-2 infection. Understanding the primary mechanism may also drive long-term development of new therapeutics that are more potent.”

[Dr. Robert Wallace Malone (born 1959)] has been working with a team of scientists to get a better understanding of just how famotidine might be working. Results of his team’s study, which have not yet been peer reviewed, appeared on a preprint server on May 23 (Research Square 2020, DOI: 10.21203/rs.3.rs-30934/v1).

Like the NCATS work, the team’s tests showed that famotidine has no effect on SARS-CoV-2’s papain-like protease, nor does it kill the virus. Instead, Malone and colleagues think the drug is working through its usual target—histamine H2 receptors. Famotidine treats heartburn by blocking H2 receptors, which when activated by histamine stimulate cells in the stomach to secrete acid.

Joseph Conigliaro, chief, General Internal Medicine, Northwell Health :  "As a physician, I can’t tell people ‘go out and buy famotidine and if you start getting an inkling of anything start taking it.’ "

But H2 receptors aren’t just in the stomach—they’re all over the body. Malone and colleagues argue that COVID-19 is disrupting mast cells, which release histamine and other signaling molecules in response to an inflammatory or allergic reaction. These cells can be found at the boundary between tissue and an external environment. They’re on the skin and line the gut and lungs. Malone reasons that mast cells could be responsible for the overactive immune response, often described as the cytokine storm, which does damage to patients with severe cases of COVID-19. By blocking the histamine that mast cells release, famotidine can dampen some of that response.

If famotidine is effective in COVID-19, why isn’t the other commonly used H2 blocker, cimetidine? The answer, Malone claims, comes down to pharmacokinetics: famotidine makes it into the bloodstream more readily than cimetidine.

Adrian M. Piliponsky, an immunologist at Seattle Children’s Research Institute who studies mast cells, says that it’s possible mast cells are playing a role in the inflammatory response to COVID-19. He notes that mast cells play a role in infections with other viruses. He thinks the idea proposed by Malone and colleagues merits further study, and he’s interested in seeing the results of the clinical trial.

[Dr. Robert Wallace Malone (born 1959)] also would like to see a comprehensive trial of famotidine in people who are in the early stages of COVID-19. But he doesn’t think the drug alone will resolve the world’s COVID-19 pandemic. “We’re committed to trying to create an outpatient cocktail of drugs that will significantly reduce morbidity and mortality for COVID-19 and have it ready for deployment in the fall,” he says.

In the meantime, doctors are urging caution for people who might see these early results and rush out to stock up on Pepcid. Carl J. Lavie, medical director of cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute, recently cowrote a letter to the editor of Mayo Clinic Proceedings encouraging doctors to wait for the clinical trial results.

He tells C&EN that it’s premature to recommend famotidine just for COVID-19, but he adds, “I also think that it is benign, so it would seem very reasonable to use for upper GI symptoms now” before giving other heartburn drugs like omeprazole.

1. CORRECTION :   This story was updated on June 16, 2020, to correctly characterize famotidine as a histamine-H2-receptor antagonist, not an agonist.

2. CORRECTION :   This story was updated on June 22, 2020, to correctly identify the group that did a virtual docking study. It was chemists at Molecular Forecaster, not [DOMANE].

A nearly $21 million government-funded study to see if a popular, over-the-counter heartburn medication could be a COVID-19 remedy has fizzled amid allegations of conflicts of interest and scientific misconduct, according to interviews, a whistleblower complaint and internal government records obtained by The Associated Press.

In mid-April, the Trump administration funded a study of famotidine, the main ingredient in Pepcid, despite a lack of published data or studies to suggest heavy doses would be effective against the novel coronavirus. When government scientists learned of the hastily produced proposal to spend millions in federal funding on the research, they considered it laughable.

Now, the Pepcid project faces an uncertain future. Northwell Health, the New York health care provider hired to conduct the testing at its hospitals, put the trial on hold due to a shortage of hospitalized COVID-19 patients in that state. Northwell is partnered with Alchem Laboratories, the Florida-based pharmaceutical company that received the contract.

The Pepcid project underscores what critics describe as the Trump administration’s casual disregard for science and anti-corruption rules — regulations meant to guard against taxpayer dollars going to political cronies or funding projects that aren’t based on more rigorous science.

It was harshly criticized by a government whistleblower, Rick Bright. He filed a complaint accusing a senior administration health official of rushing the deal through without the scientific oversight necessary for such a large federal award.

The government had very little data on which to base a funding decision about Pepcid and COVID-19, critics say; there was no high-grade research on famotidine’s coronavirus-fighting potential to underpin a clinical trial involving hundreds of patients.

“The evidence used to support the trial is extremely weak,” said Dr. Steven Nissen, a Cleveland Clinic cardiologist and a frequent adviser to the Food and Drug Administration. “And I’ve been very critical of this approach to the COVID-19 epidemic, which I’ve likened to throwing spaghetti at the wall and seeing what sticks. I consider trials like this one to be largely a waste of time and money.”

Northwell Health spokesman Matthew Libassi declined to comment on Bright’s whistleblower complaint. “With respect to the famotidine trial, we are confident it is based on sound science,” he said.

Meanwhile, two researchers are locked in a dispute about how the project came to be and who should get credit for the idea.

Dr. Robert Malone, a molecular virologist who was Alchem’s chief medical officer when it won the Pepcid contract, says he was the first to come up with the idea that Pepcid might be effective against COVID-19.

He says he got a call on Jan. 4 from a fellow American doctor working in China, Michael Callahan, who told him about the new virus causing severe respiratory illness. Malone then ran the virus’s genetic sequence through computer models designed to find already-approved drugs that might work to thwart the virus, he said. Famotidine turned up as a promising lead.

Callahan, who had been working in Wuhan, China, separately claimed he saw data indicating famotidine’s potential in COVID-19 patients, according to promotional materials about a potential Pepcid trial. But Callahan, described by Science Magazine as the “first to call attention to the drug in the United States,” never publicly produced any data from his time in Wuhan, according to Malone.

Callahan did not respond to requests for comment.

But Callahan pitched the idea to a key Trump appointee, Dr. Robert Kadlec, assistant secretary for preparedness and response at the Department of Health and Human Services.

On March 20, Kadlec wrote to Northwell’s executive vice president for research, telling him to work with Callahan to prepare a contract proposal and a draft budget for the Pepcid trial.

Federal pandemic response scientists at HHS’ Biomedical Advanced Research and Development Authority, or BARDA, were shut out of these early conversations over famotidine. Rick Bright, BARDA’s director at the time, would later file a whistleblower complaint alleging unethical conduct by agency leadership, and point to the Pepcid trial as a key example.

“By directing a member of his staff (Callahan) to work as an agent of both the company and the government regarding the proposal, Dr. Kadlec was inviting violations of federal procurement law,” Bright said in his complaint.

Kadlec did not respond to questions about Bright’s allegations, but an HHS spokesperson said senior federal executives often seek expertise both inside and outside of the government. “In that regard, Kadlec is no different,” the department’s spokesperson said in an email.

But two other federal scientists on Bright’s team shared his worries that Callahan’s involvement appeared to be a conflict of interest. Several of them initially saw the Pepcid proposal as a joke; the request was based purely on anecdotal evidence for a trial that would cost millions and take months.

Their concerns were ignored, according to Bright’s complaint and government records. Kadlec oversees Bright’s agency and wanted the Pepcid contract approved — fast.

Soon, Bright was reassigned to a lesser role in government.

In late March, the FDA expressed concerns over the famotidine dosage patients were to receive intravenously but agreed to approve the trial after Northwell said it would reduce it, records show. But a senior agency official said the reduced dosage still pushed the levels “to the limits” when compared to previous clinical tests and toxicology studies in animals.

Still, the fast-moving Pepcid proposal had snared the interest of top leadership at HHS, including Secretary Alex Azar, according to the internal emails. After Callahan and Northwell looped in Azar and other top administration officials, however, FDA approved the trial quickly, internal emails show.

Experts who conduct clinical trials said this Pepcid study would not have been funded under ordinary, non-pandemic circumstances

“We don’t have enough small studies to show that this is a drug worth pursuing,” said Dr. George Abraham, chair of the American Board of Internal Medicine’s infectious disease group.

Malone resigned as Alchem’s chief medical officer the week the company got the testing contract. He complained of a difficult work environment, and has since been critical of Callahan and the project.

“The Northwell trial is just a zombie at this point,” Malone said. “Completely irrelevant, except in a negative sense.”

Still, Kadlec said through a spokeswoman he would choose to fund the trial again. “If it could save lives, yes.” 

An over-the-counter heartburn remedy probably won’t directly stop coronavirus infections, a new study suggests.

Anecdotal reports from China suggested people hospitalized with COVID-19 who were taking famotidine (sold under the brand name Pepcid) had better outcomes than people who took a different type of antacid called a proton pump inhibitor. But famotidine has no direct antiviral activity against SARS-CoV-2, the virus that causes COVID-19, according to preliminary results reported July 15 at bioRxiv.org.

Those findings, which have not been reviewed by other scientists yet, suggest famotidine won’t help prevent coronavirus infections or illness. But they don’t rule out that the drug might help in other ways, says Mohsan Saeed, a virologist at Boston University School of Medicine. “We’re not challenging that famotidine might help,” he says. “We’re saying that the mechanism of action is not antiviral.”

The result isn’t a complete surprise. “A compound of this nature having any role in infectious disease is kind of a head-scratcher,” Saeed says. But a couple pieces of evidence had hinted that it might help against the virus.

Besides the reports out of China, two studies using computer simulations of coronavirus proteins predicted that famotidine might dock with and inhibit important viral enzymes called proteases that help the virus replicate. Based on those findings, Northwell Health in the New York City area began a clinical trial to test the antacid against the coronavirus in people.

“We were kind of surprised, because there is no laboratory evidence to show that this compound might have some effect,” Saeed says.

The data that originally suggested benefits from famotidine aren’t strong enough to justify basing treatments on the drug, says Tobias Janowitz, an oncologist and biomedical scientist at Cold Spring Harbor Laboratory in New York, who was not involved in the study. “Everything that has been published so far cannot be considered evidence for clinical efficacy,” he says. That includes a small study Janowitz was involved in which also found hints that over-the-counter Pepcid might improve symptoms for some people diagnosed with COVID-19.

Just “because a statistical association exists in these anecdotal reports doesn’t mean it is actually doing anything,” Shmuel Shoham, an infectious disease specialist at Johns Hopkins Medicine said June 26 during a news conference announcing the Infectious Diseases Society of America’s revised treatment guidelines. The infectious disease society doesn’t recommendtaking famotidine as a coronavirus treatment outside of a clinical trial.

To test famotidine’s antiviral activity, Saeed teamed up with Ali Munawar, cofounder and chief executive of Boston-based Bisect Therapeutics, Inc. Munawar’s lab did two different biochemical analyses to test whether Pepcid can bind to viral proteases as the computer simulations had predicted. Neither test showed any sign of binding.

But it was still possible that the antacid might work in other ways against the protease enzyme. So the team conducted separate analyses of enzyme activity which found no protease inhibition at all.

The team also tested whether famotidine could stop the coronavirus from infecting monkey cells or human lung cells grown in lab dishes. “We did not see any effect on viral infection,” Saeed says. By comparison, the antiviral drug remdesivir “nicely inhibited viral replication,” he says (SN: 7/13/20).

While the work has not yet been vetted by other scientists for publication in a scientific journal, the results are in line with unpublished findings from Janowitz’s Cold Spring Harbor colleagues Leemor Joshua-Tor and Nicholas Tonks who found that famotidine doesn’t inhibit the proteases as predicted, he says.

Researchers say there is still a chance that famotidine might help slow the hyperactive immune system reactions known as cytokine storms, which do damage in some severely ill COVID-19 patients (SN: 7/2/20).

“We’re not shutting the door on this being an effective therapy,” Shoham said, but doctors should not prescribe the drug to treat COVID-19 and people should not take over-the-counter Pepcid as a coronavirus remedy. The antacid needs further study in randomized clinical trials, he said. Janowitz and colleagues are planning just such a trial.

CITATIONS

M. Loffredo et al. The effect of famotidine on SARS-CoV-2 proteases and virus replication. Biorxiv.org. July 15, 2020. doi: 10.1101/2020.07.15.203059

BELOIT — “Critical care is where you go to either live or die. My job is to do my best to make sure that (you) live.”

That’s how Brittney Troxel, an inpatient critical care nurse at Beloit Health System, described her role in caring for COVID-19 patients.

Her role, along with hundreds of other Beloit Health System doctors, nurses and support staff, was turned upside down starting in March as the world grappled with a deadly virus with no known cure.

“I was no longer taking care of patients after open heart surgery, battling sepsis, suffering a cardiac event, or critical post-operative patients,” Troxel said. “Instead I was battling a monster that was foreign to me, that did things to the body that I had never seen before, that caused otherwise healthy individuals to need lifesaving care.”

COVID-19 came to the Stateline Area’s front door, wreaking havoc on daily life as schools closed, businesses shuttered and people scrambled to make sense of something not seen in a century: A global pandemic.

“The world woke up to a viral infection that had impact on lung function and extra-pulmonary effects that hits multiple systems in the body,” said Dr. Joseph Kittah, the health system’s lead intensivist and pulmonologist who has attended to all COVID-19 patients at the hospital.

Before the health system converted a critical care detachment into a COVID-19 unit with an adjoining COVID-19 floor, Kittah, along with Infectious Diseases Specialist Dr. Vijaya Somaraju, knew the virus was coming—and fast.

“We did in-house training for nurses, technicians and providers as to what to do,” Kittah said. “The administration was able to get personal protective equipment (PPE) in good time and we had a flow put together as to how to bring patients who where either confirmed or suspected cases.”

A testing site opened at the Beloit Memorial Hospital campus in March and hospital staff were shifted from their usual roles to handle the health system’s COVID-19 response.

Beloit Health System nurse Stephanie Wicks, who works in the Beloit Memorial Hospital Emergency Department, called the ED “the first line of defense for illnesses, accidents, and any number of things in between.”

Wicks said “many aspects” of the ED changed with the onset of COVID-19, noting that staff are trained within their scope of practice to be able to provide care to patients.

“The basis of how we care for patients hasn’t changed, we still approach each patient prepared to address and care for their needs,” Wicks added. “What has changed is being more diligent in assessing for symptoms that could be related to COVID-19 and making sure to ask the right questions and perform thorough assessments to identify things the patient themselves may not be aware of.”

COVID-19 humbled doctors around the world, forcing health care experts to “go back to basics” in terms of critical care management and patient care, Kittah said.

“It’s been a steep learning curve, but we’ve learned a lot about the disease and I think we better understand it now from three months ago,” Kittah said. “I think that right now from how the workflow is designed; how the ICU is organized; how our nurses care for these patients; we are beginning to be able to anticipate patient needs. The teamwork has been remarkable and the outcomes we see here are a reflection of the kind of work that we’ve learned from this disease.”

Nine Beloit residents have died due to COVID-19 as of July 13, but Kittah says the health system is bucking a national trend of seeing spiking death counts, something he directly attributes to the teamwork of the entire health system.

Kittah recalled a female patient who has been in the COVID-19 ICU unit the longest—over two months—that is now “thriving” after being placed on a ventilator twice. Those on the COVID-19 unit adapted to an unforgiving cycle of twists and turns as patient conditions worsened as their bodies attempted to fight off the virus.

“As a critical care physician, you thrive on reward and the positive reward and positive outcomes keeps you going,” Kittah said. “She had written her last words. She thought she was going to die, but she made it. That is rewarding to see that the strategies we have in place work and she’s alive today in part because of them. That’s what we live for and we hope to continue to make an impact on these patients.”

Troxel highlighted the fragility of the condition COVID-19 patients were in, saying, “We saw otherwise healthy patients teeter tottering on the plane of the living and that of the dead. The condition of the patient could change from stable to life threatening in seconds.”

As critical care units in the Stateline Area and around the world continue to care for critically ill patients, work on a vaccine is underway, but the path for any immunization will be lengthy and require countless hours of research, Somaraju said.

Somaraju added it could take 12 to 18 months or more for a vaccine to reach public distribution.

“In a normal time, vaccines aren’t released for three to five years,” Somaraju said. “In a crisis, that can be minimized down to that shorter time frame, but that takes a lot of scientific knowledge and so much goes into that. I think we have the technology and all the science is there, but testing trials is where I think the real challenge will be.”

On July 14, the National Institute of Health announced that an experimental COVID-19 vaccine was “generally well tolerated” by healthy adults in a 45-person study, according to interim results published in the New England Journal of Medicine.

Work fighting the virus in the Stateline Area is far from over, Kittah said.

“By no means is this virus gone,” Kittah said. “This is by no means over. We still have cases coming in seemingly every day. We still have patients in the ICU right now. We anticipate going into the fall it’s a possibility to see an uptick in the number of cases but we are better situated to deal with this virus.

“Don’t think about just yourself. This goes beyond the end of it all. We have to have a team approach to this thing. The least the community can do is adhere to basic principles of pandemic control by masking, physical distancing and proper hand hygiene.”

Even when the incidence of COVID-19 slows down, Kittah said the implications of combating a pandemic will have changed the U.S. medical community.

“I think there’s been a fundamental change in the way we practice medicine in this country,” Kittah said. “I’ve seen how COVID has restructured medicine generally. From how we do research, how we care for patients, even learning to protect ourselves to care for these patients. Research has moved quite a way. It’s touched the way we practice medicine.”

If there’s COVID-19 in the Beloit area, healthcare and frontline workers will continue to selflessly care for the public.

“I was never afraid to work in the COVID unit,” Troxel said. “When I was asked to go there I didn’t even give it a second thought. I knew that people needed help and I was in a position to help them, but I was fearful that I would bring COVID home to my family.”

All Beloit Health System staff interviewed by the Beloit Daily News said everyone should take responsibility to practice basic public health guidelines like social distancing, wearing a mask and hand-washing.

“These things you feel that someone has taken your rights away, but when you see that these are important things to build back the economy and build back that autonomy, if we all practice these things we will come out of this with flying colors,” Somaraju said.

“I would definitely recommend that you take precautions when you are out in public,” Troxel said. “Please wash your hands and use hand sanitizer. Try not to touch your face and mouth and wear a mask if you are able.”

Famotidine is an exquisitely specific inverse agonist of the human histamine H2 receptor. This agent is primarily administered as a treatment for gastroesophageal reflux disease (GERD) and related foregut disorders attributable to acid hypersecretion. Early in the COVID-19 outbreak, multiple research groups employing computational docking algorithms (computer programs that predict the interactions between small molecules and proteins at the atomic level) identified famotidine as a potential competitive inhibitor of both principal proteases expressed by the novel human coronavirus SARS-CoV-2. These groups posited that this remarkably safe, inexpensive, off-patent (generic) drug might directly inhibit replication of SARS-CoV-2, providing clinical benefit for COVID-19 patients. Subsequent non-clinical bench research has clearly demonstrated that famotidine does not bind to either protease to a significant extent and does not inhibit SARS-CoV-2 replication (see [1] for summary). Many of the unique clinical symptoms observed during the early phase of COVID–19 are consistent with known effects of histamine release. Most likely, if famotidine reduces the severity for COVID-19, it acts via its antagonism or inverse agonism of histamine signaling and arrestin-biased activation [1]. Multiple retrospective studies, case series, or reports have since been performed seeking to clarify whether famotidine treatment improves clinical outcomes in outpatient or in newly admitted inpatient cohorts suffering from COVID-19 disease. In some retrospective analyses, significant benefit has been reported, while others conclude no benefit.

In this issue of Digestive Diseases and Sciences, Drs. Sun, Chen, and colleagues report the first rigorous metaanalysis of data abstracted from peer-reviewed and published retrospective studies available up to the time of analysis (October 2020) [2]. Their findings clearly establish that famotidine administration at the standard GERD treatment doses (20–40 mg/day) does not provide a significant benefit in reducing the risk of serious illness, death, and intubation for hospitalized COVID-19 patients. Although not available to Sun, Chen et al. at the time of their analysis, an independent retrospective study by the Janssen/Johnson & Johnson team of Drs. Shoaibi, Fortin et al. [3] has further confirmed and extended these findings.

Retrospective analyses of clinical datasets are one of the most powerful tools available to rapidly test whether drug repurposing “hits” have clinical merit. The retrospective analysis approach is straightforward, and the logic is compelling: If a repurposed candidate can be identified, and the pharmaceutical is prescribed at sufficient frequency (for another indication such as GERD) in patients suffering from a disease (such as COVID-19), then a retrospective analysis may be useful. As clinical patient data accumulate, sufficient cases exposed to both the repurposed drug candidate and the disease may support analysis of potential association. Nevertheless, this approach presumes that the dosing regimen (timing, route, and level) for the common indication (GERD) is within the therapeutic window required for the hypothesized new clinical indication (COVID-19). To illustrate, it is unrealistic and naïve to assume that the dosing regimen for an over-the-counter indication would be the same as for a life-threatening hyper-inflammatory response to a novel infectious pathogen since the dosing, pharmacokinetics, and pharmacodistribution recommended for the licensed indication may not align with that required for the repurposed clinical indication.

To avoid artifacts, retrospective propensity score analysis requires sufficient knowledge of confounding variables in order to support statistical correction and adjustment. For example, in the case of COVID-19 and patients with GERD, one might assume that patients receiving first-line therapy with proton pump inhibitors (PPI) and also suffering from COVID-19 might serve as a valid control population for patients receiving second-line GERD therapy (famotidine). Such assumptions may not withstand the test of time, as is the case with PPI [4, 5], which thereby introduced artifacts into at least one relevant retrospective analyses [6]. Therefore, the promise and potential value of retrospective analyses for evaluating repurposed drug candidates must be viewed with caution.

The story of how famotidine became a priority drug repurposing candidate for COVID-19 began with SARSCoV- 2 infection of a physician/scientist leading one of the computational docking teams focused on the papain-like protease of SARS-CoV-2. This occurred during a Cambridge Mass drug discovery conference immediately after the Biogen super-spreader event (late February 2020). Having developed COVID-19 disease, the investigator began self-administering famotidine, which the team had identified as a therapeutic PLpro inhibitor candidate. Famotidine provided almost immediate improvements in the symptoms of shortness of breath and lung “burning.” The investigator self-titrated to 60 mg oral administration three times daily, discontinued treatment after seven days, experienced renewed symptoms and then re-initiated treatment for an additional seven days. The investigator and team had been working closely with personnel employed by both the US DoD and HHS on identifying repurposed drug candidates for COVID-19 and reported the findings to US government officials within both agencies. The office of the US Health and Human Services (HHS) Assistant Secretary for Preparedness and Response (BARDA) elected to fund a clinical inpatient trial of famotidine as a potential COVID-19 therapeutic. Original plans to perform an intravenous dose ranging study in newly hospitalized patients were scrapped when the institutional review board insisted on including hydroxychloroquine in the treatment arms (NCT04370262). After enrollment was initiated, changes in standard of care, Good Clinical Practice (GCP) audit irregularities, and failure to enroll adequate numbers of patients compromised that study (now listed as completed); as a likely consequence, results have yet to be reported. Unfortunately, since other randomized clinical trials were postponed while awaiting the results of this HHS-funded study, a prospective randomized dose-ranging single agent study may never be performed.

A modest case series report from an affiliated outpatient study (NCT04389567) concluded that optimal symptomatic relief from COVID-19 required famotidine be administered at 60 mg PO three times a day, as had been initially observed. Higher dosage levels are also supported by detailed examination of the mechanism of action, pharmacology and pharmacokinetics of famotidine as a potential COVID-19 therapeutic [1].

At this time, neither adequately powered prospective randomized clinical trials nor retrospective studies have examined whether famotidine administered at 60 mg PO thrice daily or above provide clinical benefit, but this dosage level or above has nevertheless gained informal acceptance worldwide due to anecdotal positive clinical responses and practicing physician referrals.

Drs. Sun, Chen, and colleagues have established that the standard GERD famotidine dose of 20-40 mg PO per day does not provide clinical benefit for COVID-19 disease in hospitalized patients. Unresolved is whether higher famotidine dosage levels predicted to mitigate histamine H2-receptor-mediated effects during SARS-CoV-2 infection can provide clinical benefit in similar patient populations. Unfortunately, since virtually all leading research groups employing famotidine in treatment protocols have migrated to multi-agent strategies [7–9], the baseline efficacy and effectiveness of high-dose famotidine as a single agent for treatment of COVID-19 may never be known.

Reference

1. Malone RW, Tisdall P, Fremont-Smith P, et al. COVID-19: famotidine, histamine, mast cells, and mechanisms. Frontiers in Pharmacology. 2021 (in Press).
2. Sun S, Chen Y, Hu L, Wu Y, Liang, M, Ahmed MA, Bhan D, Guo A, Yang H, Zuo Y, Yan Y, Zhou Q. Does Famotidine reduce the risk of progression to severe disease, death, and intubation for COVID-19 patients? A systemic review and meta-analysis. Digestive Diseases and Sciences. (Epub ahead of print). doi: https://doi.org/10.1007/s1062 0-021-6872-2.
3. Shoaibi A, Fortin S, Weinstein R, Berlin JA, Ryan P. Comparative effectiveness of famotidine in hospitalized COVID-19 patients. American Journal of Gastroenterology. 2022 (in Press).
4. Lee SW, Ha EK, Yeniova A, Oet al. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching Gut. 2021;70:76–84.
5. Almario CV, Chey WD, Spiegel BMR. Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors Am J Gastroenterol. 2020;115:1707–1715.
6. Freedberg DE, Conigliaro J, Wang TC et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study. Gastroenterology. 2020.
7. Kory P, Meduri GU, Iglesias J, Varon J, Marik PE. Clinical and scientific rationale for the “MATH+” hospital treatment protocol for COVID-19. J Intensive Care Med. 2021;36:135–156
8. Hogan RB, Hogan RB, Cannon T, et al. Dual-histamine receptor blockade with cetirizine—famotidine reduces pulmonary symptoms in COVID-19 patients. Pulmonary Pharmacology & Therapeutics.  2020:101942.
9. Tomera KM, Malone R, Kittah JK. Hospitalized COVID-19 patients treated with celecoxib and high dose famotidine adjuvant therapy show significant clinical responses Frontiers in Pharmacology.   2021 (in Press).

FORT BELVOIR, Va. - The COVID pandemic took the world by surprise. Researchers were left scrambling to devise a way to best mitigate the negative impact this disease has on global health. However, at the Defense Threat Reduction Agency (DTRA) it is common to operate in the “what if” space when it comes to potential biological threats. In fact, DTRA investments in technologies that detect, mitigate, or neutralize chemical and biological threats to the military and the nation date back more than 20 years.

“In late 2019, DTRA started a new program called Discovery of Medical Countermeasures Against Novel Entities ([DOMANE]) to address novel and emerging threats,” stated [Dr. David Michael Hone (born 1960)], Chief Scientist within the Vaccines and Therapeutics Division at DTRA. “Based on previous work, we decided DOMANE would not only focus on FDA-approved drugs but also combination therapeutics, as we believe that no single drug will be completely effective in treating new diseases. COVID-19 has provided us an opportunity to test our hypotheses using DOMANE."

DOMANE provides rapid decision-making capabilities to identify FDA-approved drugs that will most likely be effective therapeutics for COVID-19. Repurposing candidate drugs from a pool about 7,500 FDA-approved drugs to advance an effective COVID-19 therapeutic allows for a more rapid response in developing a therapeutic regimen. The end-result is a response that modifies COVID-19 in treated patients and promotes a speedy recovery.

Veklury®, which is more commonly referred to as Remdesivir, is a ribonuclease inhibitor developed by Gilead Sciences. It delivers broad-spectrum antiviral activity and has proven to be a modestly effective therapeutic for the treatment of COVID-19. Originally developed as an Ebola Zaire countermeasure, this DTRA-funded inhibitor transitioned for more advanced testing due to promising pre-clinical trials. Remdesivir inhibits viral replication in a wide variety of pathogens and was one of the first therapeutics identified in the Defense Department for repurposing to treat COVID-19. In the summer of 2020, Remdesivir received authorization for emergency use only in COVID-19 patients with continued FDA oversight.

To complement the modest therapeutic effect of Remdesivir, [DOMANE] also identified Famotidine, a COVID-19 disease modifier from Johnson & Johnson [See SARS-COV2 famotidine trials (2020)]; Pfizer’s Celecoxib, an anti-inflammatory product; and Merck’s Mectizan®, Ivermectin, an antiviral for clinical trials. To learn whether a combination of these FDA-approved drugs is more efficacious than current treatments, DTRA partnered with Quantum Leap Healthcare to conduct a clinical trial. This volunteer trial will evaluate drug combinations in COVID-19 patients who are having difficulty breathing.

DTRA also collaborated with Leidos to develop a new clinical trial prototype to evaluate new drug combinations in two clinical studies: one in COVID-19 patients who have symptoms but are still breathing without assistance and another in COVID-19 that are not displaying any symptoms.

“We believe that the evaluation of additional repurposed drugs in clinical trials will find a successful treatment option and will pave the road toward FDA-approval of a greatly improved therapeutic treatment for COVID-19 patients,” said [Dr. David Michael Hone (born 1960)].

DTRA is committed to supporting global health biosecurity efforts through continued vaccine and therapeutic discovery actions to treat COVID-19, as well as the next biological threat the nation faces.

With opinions and controversy swirling about masks, vaccinations and COVID-19, an infectious-disease expert will take questions from the public in a livestreamed meeting Wednesday afternoon.

The Rock County Public Health Department announced that Dr. Vijaya Somaraju of the Beloit Health System will take questions from 4 to 5 p.m.

Somaraju will give a brief presentation before taking questions from the audience.

A link to the Zoom meeting can be found on the coronavirus page at the Rock County Public Health Department website.

The session will also be live on the Rock County Public Health Department’s Facebook page, where viewers can ask questions in the comments section.

Those unable to attend may submit questions in advance and watch the recording on Facebook or YouTube afterward. Submit questions to COVID19 .Questions @co.rock.wi.us.

The presentation slides will also be available in Spanish, and an interpreter will be on the call for anyone who would like to ask questions in Spanish.

Somaraju has been practicing at Beloit Health System since June 2015. She is medical director of the system’s infectious-diseases department and is a board member of the county health department.

Somaraju was a clinical professor with extensive administrative, academic and clinical experience at the University of Illinois-Chicago campus in Peoria, Illinois, where she earned awards for outstanding teaching, according to the news release.