Potassium-Competitive Acid Blockers: A Step Forward in the Treatment of Acid-Related Diseases

Presenter: Carmelo Scarpignato, MD, DSc, PharmD, FRCP, FCP, FACG
Original Date: January 11, 2026

Acid suppression therapy has revolutionized the management of acid-related disorders since the introduction of H₂-receptor antagonists (H₂RAs) and proton pump inhibitors (PPIs). However, several unmet needs in anti-secretory therapy have become increasingly evident—particularly in the management of gastroesophageal reflux disease (GERD), Helicobacter pylori (H. pylori) eradication, protection against aspirin (ASA) and nonsteroidal anti-inflammatory drug (NSAID)-induced injury, and the treatment of upper gastrointestinal (UGI) bleeding. These limitations are largely due to the inability of conventional agents (H2RAs and PPIs) to achieve consistent acid suppression in all patients and, in particular, to effectively control nocturnal acid secretion. It soon became clear that a longer and more sustained acid suppression could yield additional therapeutic benefits. In parallel, growing concerns have emerged regarding the long-term safety of antisecretory drugs.

Over recent decades, new-generation PPIs have been developed, including dexlansoprazole modified release (MR) and instant-release omeprazole (IR-omeprazole). Other innovations—such as metered-release formulations (e.g., Durasec™) and novel compounds like tenatoprazole—have demonstrated superior control of intragastric pH, particularly during nighttime. The most significant advance, however, has been the introduction of potassium-competitive acid blockers (P-CABs). These agents inhibit the K⁺,H⁺-ATPase enzyme by blocking the K⁺ channel, providing food-independent, reversible, and rapid-onset acid suppression with a prolonged and consistent elevation of intragastric pH.

Currently, four P-CABs—vonoprazan, tegoprazan, fexuprazan, and keverprazan—are available, although only two are approved outside Asia. Vonoprazan is marketed in North, Central, and South America, whereas tegoprazan is currently available only in Latin American countries. Two additional compounds, linazapran glurate and zestaprazan, are under clinical development. While clinical trials in GERD have been conducted with all P-CABs, only vonoprazan and tegoprazan have been evaluated as components of H. pylori eradication regimens. Available data indicate that, in these two indications, P-CABs demonstrate comparable or superior efficacy to PPIs. Their short-term safety profiles appear similar to those of PPIs, although long-term data are still needed.

Bio:Carmelo Scarpignato graduated in Biochemistry at the University of Messina, and in Medicine and Surgery at the University of Modena in Italy. He is currently Professor of Medicine & Clinical Pharmacology at the Faculty of Health Sciences, LUdeS Lugano Campus, Switzerland & United Campus of Malta, Msida, Malta as well as Associate Professor of Gastroenterology at University of Nantes. He is also Honorary Clinical Professor at Chinese University of Hong Kong and Consultant Clinical Pharmacologist & Gastroenterologist. He has been Visiting Professor at some prestigious European and USA Universities.

Professor Scarpignato’s main research interests focus on digestive clinical pharmacology, gastrointestinal motility, and upper GI pathophysiology as well pain medicine. He has authored more than 500 publications (of which 350 are full papers or book chapters) on these topics and has also edited 28 books on clinical evaluation of GI function and on Pharmacology & Therapeutics of Digestive Diseases. He is or has been on the editorial boards of Pharmacology, Gut, Digestion, Digestive Diseases, Current Gastroenterology Reports, Alimentary Pharmacology & Therapeutics, BMC Gastroenterology, BMC Medicine, World Journal of Gastroenterology, American Journal of Pharmacology & Therapeutics, Therapeutic Advances in Drug Safety and Current Clinical Pharmacology, amongst others. He is also a Section Editor (GI and Liver Pharmacology) of Fundamental and Clinical Pharmacology and of Gastroenterology International, and has been co-Editor of two prestigious book series, Frontiers of Gastrointestinal Research and Progress in Basic and Clinical Pharmacology. Professor Scarpignato is a Fellow of the Royal College of Physicians (London), the American College of Physicians, the American College of Clinical Pharmacology, the American College of Gastroenterology and of the American Gastroenterological Association. In addition, he has been recognized Fellow of the European Board of Gastroenterology & Hepatology, besides being member of several national and international scientific societies, including the New York Academy of Sciences and the EU Academy of Sciences. After 20 years of serving as Secretary General, he is currently At-large Member of the Governing Board of the World Organization for Specialized Studies on Diseases of the Oesophagus (OESO) and Past Governor for Italy of the American College of Gastroenterology (ACG). His biography has been included into the 2009-2010 Edition of Who’s Who in Medicine and Healthcare.

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