A new technology to enable pharmaceutical companies to determine more effectively, and earlier on in clinical trials, whether an experimental drug is toxic to the heart has taken an important step toward the marketplace.

The University of Rochester Medical Center (URMC) and iCardiac Technologies, Inc. have signed an exclusive agreement to commercialize software developed by biomedical engineer Jean-Philippe Couderc, Ph.D., that provides a more accurate and reliable method to analyze data from electrocardiograms (ECG) and other types of heart monitors to determine whether a drug is toxic to the heart.

The technology consists of software known as COMPAS – which stands for Comprehensive Analysis of Repolarization Signal – that allows researchers to target and evaluate specific data produced by ECGs called the QT interval, in addition to other advanced measurements intended to identify specific risks associated with a new drug. The QT interval measures the process of ventricular Repolarization, the period between the heart's contraction and recovery phase. While the period lasts only a fraction of a second, it represents an important determinant of a drug's safety.

"Drug-induced prolongation of the QT interval is a critical indicator of toxicity," said Couderc. "We know that individuals with an abnormally prolonged QT interval are at far greater risk for developing fatal arrhythmias and sudden cardiac death. Consequently, effective and precise measurement of QT interval, which COMPAS provides, is an effective tool in the assessment of cardiovascular toxicity. Further, the COMPAS software will enable iCardiac Technologies to also focus on the development and deployment of additional ECG markers, which are even more specific and sensitive than traditional QT interval measurements for determining cardiac toxicity."

While there are several potential uses for this technology, the most immediate application is in clinical trials. Prolongation of the QT interval is the most common cause of drug withdrawal from the market and delays in regulatory approval. In the aftermath of the withdrawal of Vioxx and other Cox-2 inhibitor drugs over concerns that they may cause heart attacks or stroke, the FDA has proposed guidelines that call upon the pharmaceutical industry to develop better measurement methods for drug safety assessment.

In response, pharmaceutical companies are in the process of investing significant resources in research that will allow them to identify cardiac toxicity at early stages of drug testing. There is also a tremendous economic incentive: It is estimated that it costs, on average, $900 million to bring a new drug from the laboratory to the doctor's office. This new scrutiny impacts large classes of drugs, such as antibiotics, weight loss, anti-psychotic medications, heartburn medications, and some cancer and heart disease therapies, some of which have been pulled from the market or limited in use due to their tendency to prolong the QT interval.

COMPAS was designed to accurately identify ECG abnormalities, while taking into consideration other factors that may influence a person's heart activity, such as eating and stress. In fact, the FDA has purchased a license to the COMPAS software to evaluate its unique capabilities.

The new agreement pairs iCardiac Technologies – a newly established Rochester-based company which is positioning itself as the leader in cardiac safety analytics to support pharmaceutical, biotechnology, medical device and contract research companies – with technology developed by the University's Heart Research Follow-up Program, an international leader in cardiovascular research.

"We are extremely pleased to be working with the University of Rochester, one of the premier institutions in the world for cardiac safety," said Alex Zapesochny, president and chief operating officer of iCardiac Technologies. "The Heart Research Follow-up Program at the University of Rochester has focused on researching key challenges in this area for over 25 years and iCardiac is now positioned as a leader in this field due to the licensing of this core technology."

• About iCardiac Technologies, Inc. :   iCardiac Technologies, Inc., headquartered in Rochester, N.Y., is a leading provider of advanced cardiac safety analysis technologies. The company evolved from research carried out at the Heart Research Follow-up Program at the University of Rochester. The company's technology provides more rigorous characterization of the cardiac safety profiles of in-development and on-market drugs. This allows iCardiac's customers to both accelerate drug development as well as bring compounds forward in clinical trials with more confidence about their cardiac safety. Additionally, the company's core technology has applications in ECG-based cardiac diagnostics and medical devices.
• About URMC's Heart Research Follow-up Program :   The Heart Research Follow-up Program, which is funded in part by the National Institutes of Health, is a national and international leader in the science of heart arrhythmias and a rare genetic condition associated with an abnormal QT interval, called the congenital Long QT Syndrome (LQTS). The University keeps an International Registry for LQTS and follows thousands of families who have this inherited condition. One of the genetic forms of the QT prolongation syndrome is similar to the drug-induced syndrome, and the University's work focuses on developing the tools to identify individuals with either condition.

Medical technology firm [iCardiac Technologies] Inc. has inked a multiyear, multimillion-dollar deal with Pfizer Inc., which includes an undisclosed equity investment in the local firm.

The alliance will involve the development and validation of electrocardiogram-based biomarkers, using iCardiac Technologies’ software technology platform, Comprehensive Analysis of Repolarization Signal. Financial terms of the deal were not disclosed.

The companies Monday announced the agreement at the Cardiac Safety Assessment Summit conference in Arlington, Va.

Under the agreement, iCardiac and Pfizer will collaborate on a research program that includes a series of studies. Over the term of the alliance, iCardiac will receive an equity investment and technology license payment, and research and development funding. It will retain commercial rights to the validated technology platform and new biomarkers for future application in cardiac safety clinical trials and technologies, officials said. Biomarkers are often used to measure the effects or study the progress of a disease.

A cross-licensing arrangement will allow [iCardiac Technologies] to receive rights to ECG analysis technologies developed within Pfizer. The long-term goal of the deal is to improve the precision, increase the speed and decrease costs of cardiac safety clinical trials.

"We are extremely pleased that Pfizer has partnered with iCardiac in further developing iCardiacs suite of ECG-based biomarkers and its COMPAS platform technology for advancing the field of cardiac safety testing in pharmaceutical research and development," said [Alexandra "Sasha" Latypova (born 1971)], co-founder and executive vice president of iCardiac Technologies, in a statement.

Dubbed COMPAS, the [iCardiac Technologies] technology was developed over a decade at the University of Rochester's Heart Research Follow-Up Program. Researchers use it to analyze data from ECGs and other types of heart monitors, to test the safety and efficacy of drugs. Jean-Philippe Couderc, chief technology officer at iCardiac Technologies and assistant director of UR's Heart Research Follow-Up Program, is the principal inventor. UR last year licensed the technology to iCardiac Technologies.

"Cardiac safety is one of the most challenging hurdles in developing new medicines," said Kate Robbins, Pfizer spokeswoman. "We support the development of new tools that may enhance our ability to predict the safety of potential new medicines in early stages of research and development."

The company plans to use proceeds from the Pfizer investment to accelerate its research and validation efforts and hire staffers, Alex Zapesochny, president and chief operating officer at iCardiac Technologies, told the Rochester Business Journal. Located on Allens Creek Road in Brighton, the firm employs 17 full-time and contract staffers. Zapesochny did not disclose the number of positions, except to say “several more jobs,” will be added this year.

The firm this year plans to execute on its research goals related to the alliance with Pfizer and pursue other applications for its biomarkers.

"We're also going to see if we can get other companies besides Pfizer to also join with us as part of a broader cardiac safety alliance to further accelerate finding the solution to this problem," Zapesochny said. "And what that means is essentially development and validating the next generation of tools that will determine with more definitiveness whether or not drugs are safe for the heart or not."

The local firm is in the process of approaching the top 10 pharmaceutical companies to gauge their interest.

"We have very strong preliminary interest from five large pharmaceutical companies who want to get involved in this alliance because they all recognize the value of the next generation of tools and limitations of the current set of tools," [Alexandra "Sasha" Latypova (born 1971)] said in an interview.

The company hopes to structure a broader industry alliance within the next 12 months, she said.

Keeping hearts healthy and heard about the vaccine against human getting damaged hearts well again occupies a lot of my time. That’s one reason I am very pleased with the early success of iCardiac Technologies, Inc., one of the newly established companies based on technology developed at the University of Rochester Medical Center (URMC).

The importance of technology for future growth of URMC’s reputation and revenues will become clear in the several examples I discuss below.

iCardiac grew out of research at the Medical Center’s Heart Research Follow-up Program, a national and inter- national leader in the science of heart arrhythmias. Software developed by biomedical engineer Jean-Philippe Couderc, Ph.D., provides a more accurate and reliable method to analyze data from electrocardiograms and other types of heart monitors to determine whether a drug is toxic to the heart. This helps a pharmaceutical company decide on the fate of drugs in development and also builds confidence in the safety of drugs. Earlier this year, iCardiac entered into a multi-year research alliance with Pfizer Inc. to develop and validate advanced ECG-based cardiac safety biomarkers utilizing iCardiac’s tech- nology known as COMPAS. Pfizer also became an equity investor in iCardiac.

This is good news for the safety of drugs and protection from heart arrhythmias. But this also is welcome news for economic development. The company has 20 full-time and contract employees and expects to add more. Just as significantly, iCardiac enhances URMC’s and Rochester’s reputation for advanced analytics in the biopharmaceu- tical industry. VirtualScopics Inc., another successful company founded on technology developed at the Medical Center, helped establish that reputation.

Much of the world by now has heard about the vaccine against human papillomaviruses (HPV). This is more good news. HPV causes most cases of cervical cancer and a vaccine will save thousands of lives. Work by a trio of Medical Center virologists — Robert Rose, Ph.D., William Bonnez, M.D., and Richard Reichman, M.D.— was key to the development of the vaccine. About two years ago, the University, Merck and Co., GlaxoSmithKline, and several other parties agreed on a settlement involving patents and royalties related to a vaccine.

The University will receive royalties from the HPV vaccines. The University owns a stake in iCardiac.

As state and federal budgets get even tighter, investments in successful compa- nies become more important for the Medical Center and for the Rochester area. In fiscal year 2006, Medical Center revenues from licenses rose to an all- time high of $37.7 million, a 34 percent increase over the previous year. In the same time period, 10 new patents were awarded and 101 invention disclosures were filed. We expect growth will continue in both of these areas.

Biomedical research can provide increased financial resources for the Medical Center and opportunities for economic development in the Rochester area. We have superb physi- cians, scientists and technicians at URMC that can make this happen. The Medical Center will increase investment in the Office of Technology Transfer for two reasons. First, this will enable us to develop existing technologies more rapidly and efficiently. Second, when appropriate, start-up companies will be facilitated in Rochester. Development of technologies for software, drugs and devices is now as key component of the URMC mission.

A breakthrough by a portfolio company of Norwest Venture Partners has the firm's heart aflutter.

iCardiac Technologies Inc., a provider of cardiac safety assessment services, in the fall completed a study in collaboration with the U.S. Food and Drug Administration that demonstrated cardiac toxicity in drugs can be detected much earlier in the development process than previously thought by medical professionals.

The results of the study were released during an FDA-hosted cardiac safety research consortium meeting Friday.

Norwest, which invested in the company in March, said it expects the market that can employ iCardiac's technologies to expand significantly as a result.

iCardiac Technologies "Our investment case was that the deal would work either way, but a positive trial result transforms a very good company into a great one, from a returns basis, assuming we get the traction we expect," said Dr. Ryan Harris, a partner at Norwest, a venture capital and growth equity firm.

Cardiac safety testing is required of all compounds in development as it aims to protect patients from drugs that may prolong one's QT interval (as in the Q and T waves recorded in an electrocardiogram), a measurement used to predict a person's risk of sudden cardiac death.

Thorough QT studies, or TQTs, are routinely performed to assess QT-prolonging potentials in drugs before they end up in consumer hands.

A TQT-which may make or break a drug-development program-is employed as an independent study late in the drug development process, usually at the end of a Phase II or at the beginning of Phase III trial, when millions of dollars and much effort have been sunk into coming up with a new drug.

Alex Zapesochny, iCardiac's president and chief executive, said the new method of conducting cardiac safety testing allows such screening to be moved forward in the drug-development process by several years. The test also can be conducted concurrently in a Phase I trial, where a new drug or treatment is administered to a small group of people to evaluate its safety, determine its dosage range and identify possible side effects.

As a result, iCardiac will be able to tap a much broader base of drugs under development. Mr. Zapesochny said he expects the number of studies that can undergo the company's cardiac safety testing is estimated to post a fivefold increase.

Part of the expansion will be driven by drug makers sticking with a drug's development and not giving up on it because of uncertainties related to cardiac risks to patients. Mr. Zapesochny said cardiac safety testing is costly at about $2 million to $5 million per drug under development. He added the propensity to cause cardiac risks is often a major reason for drug makers for not pursuing development of a new drug.

"The beauty of this shift is that now, instead of unnecessarily killing drugs, there is an early, cost-effective method for pharma companies to intelligently and thoroughly assess the cardiac side effects potential of the drugs they are developing," Mr. Zapesochny said.

An article in the British Journal of Pharmacology in 2011 stated 27% of drugs didn’t make it to human trials  because of cardiovascular toxicity concerns.

iCardiac's new methodology comes at a time when the global pharmaceutical industry is in a race to develop new drugs, partly to replace the large number of old drugs that have come off patents. The Pharmaceutical Research and Manufacturers of America said in a 2013 profile  there were more than 5,400 medicines in development globally in 2011.

iCardiac executives said its technology, and the affirmation it gets from the collaborative study with the FDA, will help balance the pharmaceutical industry's need to ensure patient safety with promoting more effective drug development.

"What made cardiac safety testing so imprecise before was the significant amount of subjectivity in measuring a key indicator of arrhythmia liability. iCardiac's innovation stems from figuring out ways to reduce variability and imprecision in this key indicator," said Mr. Zapesochny.

iCardiac incorporated a vast pool of data collected in the past 25 years by the University of Rochester on the natural variability of QT intervals during its research on arrhythmias and long QT Syndrome to increase the measurement accuracy that can predict cardiac risks.

Dr. Norman Stockbridge, a director in the Division of Cardiovascular and Renal Products at the FDA's Center for Drug Evaluation and Research, said "if a pharmaceutical company comes to me with results using this type of a methodology, and the study is well conducted with high quality electrocardiogram data collection and analysis, I'm ready to recommend its use in regulatory decision making today."

Norwest's Dr. Harris said iCardiac's new methodology will benefit drug developers, particularly venture-backed ones with a limited pipeline of new drugs in development.

"In order to partner with large pharmaceutical companies, smaller drug developers often need to demonstrate cardiac safety. By making cardiac safety studies more accurate, faster and less expensive, they are more likely to test cardiac safety earlier and that will help them partner with larger pharmaceutical companies," he said.

Norwest doesn't invest in individual drugs.

The Palo Alto, Calif., firm makes venture capital and growth equity investments in the U.S. and internationally across cloud and IT infrastructure, Internet-enabled business and consumer products and services, financial services and health care.

Norwest has a single limited partner, Wells Fargo & Co. It is investing from its 12th fund, Norwest Venture Partners XII LP, which closed with $1.2 billion in May .

ERT has snatched up iCardiac Technologies, a company known for its cardiac safety services for clinical studies, just three months after it bought Biomedical Systems, which started shop in 1975 with clinical cardiac solutions.

“iCardiac has introduced several breakthrough innovations over the past decade, including High Precision QT and Early Precision QT methodologies,” said iCardiac president and CEO Alex Zapesochny, who will join ERT’s executive team to lead the cardiac safety business.

Back in 2015, the International Council for Harmonisation updated its E14 Q&A guideline, adopting an alternative path that allows data from early-stage clinical trials be used to demonstrate a noncardiac drug’s QT effect. The previous guideline, adopted in 2005, required such drugs to undergo a dedicated clinical study to ensure that the drugs don’t cause unusual QT interval prolongation, which could lead to cardiac arrhythmia.

That revision was based on a study (PDF) conducted by iCardiac with the Cardiac Safety Research Consortium. It confirms that combining ECGs and pharmacokinetic samples—the basic components of iCardiac’s High Precision QT approach—with exposure response analysis can achieve much higher precision in gauging drug candidates’ cardiac safety profiles in phase 1 trials.

Besides, iCardiac touts that its method of performing QT assessment as part of routine early-phase in-human studies only costs $150,000 to $300,000, saving developers millions of dollars as compared to $2 million to $5 million when conducting the usual stand-alone Thorough QT (TQT). So far, eight of the top 10 pharma companies, along with several mid- and small-sized biopharma firms, have signed up for its services.

Philadelphia-headquartered ERT has existing offerings in cardiac safety, so, to ERT president and CEO James Corrigan, the deal is “a natural fit.”

The company just expanded the sector three months ago with the purchase of Biomedical Systems. ERT at that time pictured the acquisition mainly as a move for Biomedical Systems’ 30-year-plus experience in imaging technology, as a further expansion from a May purchase of Cleveland Clinic’s cloud-based imaging technology to meet the industry’s growing demand for imaging data submissions per requests from regulators.

But it’s worth noting now that the Missouri-based company’s origin is actually in cardiac services. Biomedical started offering cardiac services when founded in 1975 and ran its first centralized ECG in 1979. By time of the ERT deal, it has managed more than 8,000 cardiac safety trials across the globe and offers cardiac event monitoring, blood pressure monitoring, echocardiography and TQT studies.

Both iCardiac and Biomedical provide respiratory/pulmonary solutions that accelerate clinical research and are now all part of ERT’s portfolio.