PCABs

Research evidence

These are some research papers that have so far been published on the efficacy of PCABs.

Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases (Aug 2016 Pharmacology & Therapeutics)

“Potassium-competitive acid blockers (P-CABs) inhibit H+,K+-ATPase in a reversible and K+-competitive manner, and exhibit almost complete inhibition of gastric acid secretion from the first dose. Many pharmaceutical companies have tried to develop P-CABs, but most of their clinical development has been discontinued due to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in Japan, has a completely different chemical structure and higher pKa value compared to other P-CABs, and exhibits rapid onset of action and prolonged control of intragastric acidity. Vonoprazan is an effective treatment for ARDs [Acid Related Diseases] that is especially effective in healing reflux esophagitis and for H. pylori eradication. P-CABs, such as vonoprazan, promise to further improve the management of ARDs.”

Potent Potassium-competitive Acid Blockers: A new Era for the treatment of Acid-related Diseases (Neurogastroenterology & Motility Jul 2018)

"Vonoprazan does not require enteric coating as it is acid-stable, and it can be taken without food because it is quickly absorbed. Vonoprazan accumulates in parietal cells under both acidic and neutral conditions. It does not require an acidic environment for activation, has long-term stability at the site of action, and has satisfactory safety and tolerability. Thus, vonoprazan may address the unmet medical need for the treatment of acid-related diseases."

Potassium-competitive acid blockers - are they the next generation of proton pump inhibitors? (Gastrointestinal Pharmacology & Therapeutics Dec 2018)

"Although proton pump inhibitors have been proven to be efficacious, they have a slow onset of action with limited resolution of symptoms in most patients. Potassium-competitive acid blockers (P-CABs) are novel drugs that bind reversibly to K+ ions and block the H+, K+ ATPase enzyme, thus preventing acid production. P-CABs have a fast onset of action and have dose-dependent effects on acid production. Animal studies exist that differentiate the better results of P-CABs from proton pump inhibitors."

This paper in Gastrointestinal Pharmacology and Therapeutics  from 2018 provides a very good initial overview: Potassium-competitive acid blockers - are they the next generation of proton pump inhibitors? 

"There have been tremendous changes in the treatment of acid-related diseases. In this rapidly evolving field, novel drugs such as potassium-competitive acid blockers (P-CABs) show promising potential. This review aims to provide a perspective on this new class of drugs by summarizing the mechanism of action, therapeutic benefits, adverse effects and approval status of various P-CABs in the market."

Comparison of the Use of Vonoprazan and Proton Pump Inhibitors for the Treatment of Peptic Ulcers Resulting from Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis (Medical Science Monitor Feb 2019)

"The findings of the systematic review and meta-analysis showed that the efficacy of vonoprazan was comparable with PPIs for the treatment of peptic ulcers following ESD. Further studies are required to support the safety and efficacy of vonoprazan compared with different types of PPIs. "

This study was published in Medical Science Monitor in 2019: Comparison of the Use of Vonoprazan and Proton Pump Inhibitors for the Treatment of Peptic Ulcers Resulting from Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis

"The findings of the systematic review and meta-analysis showed that the efficacy of vonoprazan was comparable with PPIs for the treatment of peptic ulcers following ESD. Further studies are required to support the safety and efficacy of vonoprazan compared with different types of PPIs. "

Efficacy of vonoprazan 10 mg compared with 20 mg for the initial treatment in patients with erosive esophagitis: a randomized pilot study (Esophagus Nov 2020)

“At 4 weeks, the endoscopic healing rates of the 20 mg and 10 mg groups were 94.6% and 94.4%, respectively. The FSSG scores of the 20 mg and 10 mg groups were significantly decreased in both treatment groups from 13 (4-39) to 4 (0-25) and 14 (4-40) to 3 (0-29), respectively. At 12 weeks, the scores further decreased to 2 (0-13) and 2 (0-26), respectively. The vonoprazan 10 mg group showed a similar therapeutic effect to the 20 mg group in mucosal healing at 4 weeks and in symptom relief throughout the study period. When stratified by esophagitis grading, these findings were still demonstrated in grade A/B patients but not in grade C/D patients.” (73 patients)

Effects of vonoprazan on gastric PH and clinical course after gastric ESD: A retrospective and prospective study (Dec 2020 Annals of Medicine & Surgery)

“There were 14 cases of post-ESD bleeding in patients treated with proton-pump inhibitors (PPIs), including oozing during second-look endoscopy compared to only 1 case of bleeding with vonoprazan administration (p < 0.05). Vonoprazan was also associated with better post-ESD ulcer healing than PPIs. Gastric pH during ESD after vonoprazan administration on the night before gastric ESD was ≥6.96 in all 11 patients. “

Review article: potassium-competitive acid blockers for the treatment of acid-related disorders (Feb 2021 Alimentary Pharmacology & Therapeutics)

“It is currently licensed in some Asian and South American countries and is being developed for North America. In clinically relevant doses, P-CABs have produced more rapid and profound suppression of intragastric acidity than proton pump inhibitors (PPIs). Vonoprazan was non-inferior to lansoprazole in healing erosive oesophagitis (2 randomised controlled trials [RCTs] in 1137 subjects) and superior in maintaining remission (1 RCT; 607 subjects). In 2 RCTs (1120 total subjects), both vonoprazan and tegoprazan were non-inferior to lansoprazole for healing peptic ulcers.”

Long-term vonoprazan therapy is effective for controlling symptomatic proton pump inhibitor-resistant gastroesophageal reflux disease (Biomedical Reports Feb 2021)

“Even with vonoprazan therapy, symptoms of GERD in the non-erosive group were refractory compared with the erosive group, and required additional treatment in a larger proportion of patients (45 vs. 13%). GERD symptoms in the non-erosive group significantly improved from baseline and remained better after 1 year of vonoprazan therapy, similar to the erosive group. In addition, vonoprazan improved epigastric pain and postprandial distress symptoms in the non-erosive group, and 1 year of vonoprazan therapy did not aggravate constipation or diarrhea. In conclusion, 1 year of vonoprazan therapy improves GERD symptoms in patients with PPI-resistant GERD.”

This study was published in Gastroenterology in October 2022: "Vonoprazan versus Lansoprazole for Healing and Maintenance on Healing of Erosive Esophagitis: A Randomized Trial"

"Vonoprazan was non-inferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis."

A study published in Cureus in 2024 reviewed papers and randomised controlled trials comparing PPIs and PCABs, concluding, "This meta-analysis demonstrates that PCABs are more effective than PPIs in healing Erosive Esophagitis and resolving heartburn symptoms in patients with GERD. PCABs showed a higher rate of healing and symptom relief while maintaining a safety profile comparable to PPIs. The superior efficacy of PCABs can be attributed to their unique pharmacological properties, allowing for enhanced acid suppression. However, long-term safety data for PCABs are still limited."

This 2024 paper compared the new PCAB, Zastaprazan with esomeprazole, Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis, concluded. "An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole."

Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study (2024) reported a randomized trial that studied the 5-year safety profile of vonoprazan compared with that of lansoprazole for the treatment of erosive esophagitis. Patients receiving daily vonoprazan had no malignant alterations of the gastric mucosa or gastric neuroendocrine tumors after 5 years. The safety profile was comparable between vonoprazan and lansoprazole. 

Although daily vonoprazan appears to be safe at 5 years based on these data, careful monitoring is recommended until additional long-term data are obtained.

This 2024 paper from Frontiers, "Fexuprazan safeguards the esophagus" looks at the mechanism of action concluding: "Our findings reveal that all p-CABs exhibit anti-inflammatory properties, while fexuprazan inhibits inflammation and pyroptosis of esophageal cells caused by the gastric acid. Therefore, it is presumed to have additional benefits in gastroesophageal reflux disease in addition to suppressing gastric acid secretion."

A 2024 Korean study published in Nature, January 2025, compared Tegoprazan vs Esomeprazole as an on-demand therapy. Potassium-competitive acid blockers (P-CABs) can act on resting proton pumps, which eliminates the need for pre-meal dosing. The authors hypothesized that P-CAB would yield higher patient satisfaction. However, the actual study results showed no significant difference between the two groups.
"Though this study did not demonstrate a substantial difference in symptom improvement or satisfaction between the esomeprazole group and the tegoprazan group, it is evident that the rapid symptom improvement observed with tegoprazan can ultimately lead to improved quality of life and increased patient satisfaction."
It concluded, "tegoprazan is effective as on-demand therapy for GERD. Tegoprazan, when used as an on-demand regimen, improves patient symptoms more rapidly when compared to esomeprazole."

A study published in Cureus in May 2025, compared the Efficacy and Safety of Tegoprazan versus Proton Pump Inhibitors for Erosive Esophagitis concluding, "Tegoprazan demonstrated comparable efficacy and safety to PPIs in the treatment of erosive esophagitis. Meta-analysis of four Randomised Contol Trails (RCTs) revealed no significant differences in the healing rates at both four and eight weeks, with similar safety profiles between both treatment groups. The findings of previous studies, including network meta-analysis, showed non-inferiority of PCABs, including tegoprazan, in comparison to PPIs."

From MD Edge January 2025, AGA Clinical Practice Update: P-CABs Can Help When PPI Therapy Fails, "Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

"However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs."

From Cureus May 2025, Comparing Proton Pump Inhibitors and Emerging Acid-Suppressive Therapies in Gastroesophageal Reflux Disease: A Systematic Review, "The evidence from recent RCTs [Randomised Control Trials] supports the efficacy and safety of emerging acid-suppressive therapies, including P-CABs and mucosal protective strategies, as viable alternatives or adjuncts to traditional PPI therapy in the management of GERD. While P-CABs such as fexuprazan and tegoprazan demonstrate comparable or faster symptomatic relief than PPIs."

PCABs and Cancer?

Whether or not PCABs demonstrate a similar chemo-protective benefit to PPIs is yet to be determined.

An association has been suggested of increased risk of Gastri Cancer after H-Pylori treatment with vonporazan.

AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice

The clinical practice update by the American Gastroenterological Association in September 2024, provides best-practice advice on the integration of potassium-competitive acid blockers (P-CABs) into clinical practice.

There was a general recommendation against the use of P-CABs as initial therapy for acid-related conditions owing to costs, challenges in obtaining P-CABs, and limited long-term safety data. 

P-CABs were recommended in place of proton pump inhibitors for the treatment of Helicobacter pylori infection in most patients.

Diagnosis by PCAB

A 2025 study concluded, "The P-CAB test (tegoprazan) presents a promising tool for the diagnosis of GERD. A one-week treatment with a criterion of 75% reduction in symptom scores from baseline may be the most cost-effective approach."

This is similar to Diagnosis by PPI frequently employed by doctors.

Page updated 28 May 2025