Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

Abstract

Purpose of the review The introduction of H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) into clinical practice has been a real breakthrough in the treatment of acid-related diseases. PPIs are now the standard of care for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), Helicobacter pylori infection, NSAID-associated gastroduodenal lesions, and upper gastrointestinal bleeding (UGIB). However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. Recent findings To address these needs, new long-acting compounds (such as tenatoprazole and AGN 201904-Z) and new PPI formulations, including instant release omeprazole (IR-omeprazole) and dexlansoprazole modified release (MR), have been developed. However, a major advance has been the development of the potassium-competitive acid blockers (P-CABs), which block the K+,H+-ATPase potassium channel, are food independent, are reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan and tegoprazan are the two marketed P-CABs while two other compounds (namely fexuprazan and X842) are under active development. Available for almost 6 years now, a considerable experience has been accumulated with vonoprazan, the efficacy and safety of which are detailed in this paper, together with the preliminary results of the other members of this new pharmacologic class. Summary Based on the available evidence, erosive reflux disease, H. pylori infection, and secondary prevention of NSAID gastropathy can be considered established indications for vonoprazan and are being explored for tegoprazan and fexuprazan. In the treatment of severe (LA C & D) reflux esophagitis and H. pylori eradication, vonoprazan proved to be superior to PPIs. Other uses of P-CABs are being evaluated, but clinical data are not yet sufficient to allow a definitive answer on its efficacy and possible superiority over the current standard of care (i.e., PPIs). The most notable indication of upper GI (non-variceal) bleeding, where vonoprazan would prove superior to PPIs, has not yet been explored. The safety of P-CABs in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

The Current Role of Vonoprazan in Helicobacter pylori Treatment

“…2 Despite broad recognition in the medical and public health communities about the increasing morbidity and mortality associated with early-onset CRC, the factors driving this increase are largely unknown. Many studies have investigated risk of early-onset CRC associated with traditional, well-known risk factors for CRC , including a Western diet, 3 heavy alcohol use, 4 tobacco use, 5 sedentary behavior, 6 obesity, 7,8 and diabetes. 7 In this issue of Gastroenterology, Jin et al 9 continued this line of research by using the South Korean National Health Insurance Service database to conduct a cohort study of more than 5.7 million adults ages 20-49 years and more than 4.1 million adults aged 50 years investigating the association of obesity and metabolic syndrome with early-onset CRC.…”

“…3 Vonoprazan is a potassium competitive acid blocker with stronger and longer lasting reduction of gastric acid secretion than PPIs. 4 Higher acid suppression has been shown to be associated with successful eradication of H pylori with triple therapy. 5 Vonoprazan combined with amoxicillin and clarithromycin (VAC) has also outperformed PAC in trials conducted in Asia confirming this theory.…”

A Population Pharmacokinetic Model of Vonoprazan: Evaluating the Effects of Race, Disease Status, and Other Covariates on Exposure

“…Vonoprazan is a potassium‐competitive acid blocker that has demonstrated rapid, potent, and long‐lasting gastric acid suppression 1–3 . It has been approved in Japan and 14 other countries in Asia and South America for a number of years for the treatment of a variety of acid‐related diseases 4,5 . Its principal use is in the management of gastroesophageal reflux disease.…”

“… 1 , 2 , 3 It has been approved in Japan and 14 other countries in Asia and South America for a number of years for the treatment of a variety of acid‐related diseases. 4 , 5 Its principal use is in the management of gastroesophageal reflux disease. The 2 main subtypes of gastroesophageal reflux disease are erosive esophagitis and nonerosive reflux disease.…”

Editorial: slow progress to optimising H. pylori eradication treatment with antisecretory drugs

“…However, studies confirm that strong, long‐lasting acid inhibition, especially at night, is critical for H. pylori eradication 9 . The promising initial results with vonoprazan‐based dual therapy 10 build on these objectives and offer enhanced compliance, low amoxicillin resistance rates, avoidance of clarithromycin, and infrequent adverse events.…”