Only recently did I hear about a new class of drugs that shows effectiveness in controlling GI problems that are difficult to treat. The new drug class is called potassium-competitive acid blockers, and they have shown efficacy in the treatment of erosive esophagitis, symptomatic gastroesophageal reflux, gastric and duodenal ulcers, and Helicobacter pylori bacterial infection. The gold standard of treatment for these disorders has evolved over the past 50-60 years. When I was a medical student and intern, peptic ulcer disease, and any acid-related disorder, was treated with acid restriction and various diets that reduced acid production. All sorts of antacids and oral acid neutralizers were prescribed, but with minimal success. After I started practice, Histamine-2 (H-2) blockers—cimetidine, ranitidine, famotidine—came along and provided symptom improvement but had little effect on ulcer healing. In the 1980’s or ‘90’s, proton-pump inhibitors (PPI’s)—omeprazole, lansoprazole, esomeprazole—appeared on the market and were very well-received. PPI’s reduced hydrochloric acid secretion far more effectively, but had a quirk in their kinetics that caused a subgroup of patients to be resistant to their effects. Doctors were warned to use them short-term (2 weeks or less) because there was concern the degree of hydrochloric acid reduction could lead to higher rates of stomach cancer. None of these was the perfect drug!
Last on the scene were the topic of this discussion, potassium-competitive acid blockers—vonoprazan , tegoprazan, keverprazan—which are a new drug class. P-CAB’s bypass the limitations of H-2’s and PPI’s, are far more potent, and have a more “rapid onset [of action] and better control of acid secretion.” To maintain acid reduction and efficacy, the blood concentration of P-CAB’s must remain constant. Multiple studies have shown these drugs equal, or exceed PPI’s, in the treatment of the problems mentioned above.
Gastric acid (HCl—hydrochloric acid) is secreted by parietal cells in a part of the stomach called the gastric antrum. Acid secretion occurs in response to the intake of food. Excess hydrochloric acid and several other factors are responsible for causing gastric ulcers, GE reflux disease, erosive esophagitis, and heartburn. Helicobacter pylori bacteria were discovered to be the major factor causing peptic ulcers (gastric and duodenal ulcers). Eradicating H.pylori bacteria and controlling acid secretion are the keys to curing or preventing these problems.
P-CAB’s have been studied extensively by pharmaceutical companies in Japan and South Korea where the drugs were first introduced. The stand-out drug in the class is Vonoprazan (Voquenza). It was first approved for use in Japan and has a 93.5% cure rate for gastric ulcers. When combined with amoxicillin and clarithromycin, vonoprazin has a 94%-97% rate of eradication of H. pylori. Those are very good statistics, but are similar to statistics for PPI’s.
Vonoprazin had trouble getting regulatory approval because during trials there were significant problems with liver toxicity. In fact, development of the drugs was stopped due to hepatotoxicity. Later versions of P-CAB’s, vonoprazin in particular, have fewer side effects and have solved the liver toxicity problem so safety is not an issue. Efficacy compared to PPI’s has been studied extensively:
Vonoprazan is superior to lansoprazole (Prevacid-a PPI) for maintaining healing of erosive esophagitis.
Vonoprazan “improves epigastric pain, post-meal distress/indigestion, constipation, and diarrhea similar to esomeprazole (Nexium-a PPI).”
Vonoprazan has similar efficacy in healing of gastric and duodenal ulcers to lansoprazole.
Vonoprazan “combined with amoxicillin and clarithromycin or metronidazole is effective for eradication of H. pylori.” Results were superior to those of lansoprazole.
Vonoprazan was “superior to PPI’s in inhibiting acid secretion, but was equally effective in the treatment of endoscopic submucosal dissection (a tear in the esophagus).”
Vonoprazan is effective for preventing NSAID-induced ulcers.
Vonoprazan is “well-tolerated and produced a rapid, profound and sustained suppression of gastric acid secretion.”
P-CAB’s showed better rates of healing for erosive esophagitis at 4 and 8 weeks compared to both PPI’s and placebo. Keverprazan 20 mg had the highest healing rate at 8 weeks and Vonoprazan 40 mg had a “relatively higher healing rate at 4 weeks….Most P-CAB’s showed a higher healing rate than PPI’s….may help future directions of treatment.”
Vonoprazan is Voquenza.
Dr. G’s Opinion: P-CAB’s have received little or no hype. I’ve never seen one advertised nor heard of one being prescribed. The studies show they are effective, but they were slow to gain FDA approval. I found no information on cost so maybe that’s a reason the drug class has received little attention. Liver toxicity may be a reason, also. However, improved healing rates for erosive esophagitis and peptic ulcers and excellent eradication of H. pylori should be enough to gain prescribers’ attention.
References: Simadibrata DM, Syam AF, Lee YY. A comparison of efficacy and safety of potassium competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis. J Gastr Hep 2022;37:2217-2228.
Rawla P, Sunkara T, Ofosu A, Gaduputi V. Potassium-competitive acid blockers—are they the next generation of proton pump inhibitors. World J of Gastro Pharm and Therapeutics 2018 December 14; 9(7):63-68.
Simadibrata DM, et al. A systematic review with meta-analysis: Efficacy and safety of potassium-competitive acid blocker compared with proton pump inhibitor in the maintenance of healed erosive esophagitis. JGH Open 2024;8:e13053
Onge ES, Phillips B. Vonoprazan: A new potassium-competitive acid blocker. J Pharm Tech 2023;39(3):139-146.
Sue S, Maeda S. Is a potassium-competitive acid blocker truly superior to proton pump inhibitors in terms of Helicobacter pylori eradication? Gut Liver 2021 November 15;15(6):799-810.
Kumar S. Acid blockers appear superior to PPI’s in erosive esophagitis. Medscape Medical News 2024 August 8.
