Potassium-Competitive Acid Blockers in GERD and Helicobacter pylori Infection: The Emerging Role of Fexuprazan

The pharmacological control of gastric acid secretion has evolved substantially over the past five decades, yet clinically important limitations remain with delayed-release proton pump inhibitors (PPIs), including delayed onset of action, meal dependency, nocturnal acid breakthrough, and variable intragastric pH control. Potassium-competitive acid blockers (P-CABs) represent a major advance in antisecretory therapy by providing rapid, potent, sustained, and meal-independent inhibition of the gastric H+,K+-ATPase through a reversible mechanism of action. Among currently available P-CABs, fexuprazan is a relatively recent agent for which an expanding body of pharmacological and clinical evidence has become available. This review critically examines its pharmacology, experimental biology, and clinical efficacy, with particular emphasis on gastroesophageal reflux disease (GERD) and Helicobacter pylori infection. Randomized controlled trials and real-world studies demonstrate that fexuprazan is non-inferior to esomeprazole in healing erosive esophagitis, with evidence of rapid symptom improvement, effective nocturnal symptom control, and greater dosing flexibility. Emerging data also suggest potential benefit in extra-esophageal manifestations of GERD. Experimental studies indicate anti-inflammatory, antioxidant, and epithelial barrier-protective properties, although their clinical relevance remains to be established. In H. pylori infection, the profound and sustained intragastric pH elevation achieved with P-CABs may enhance eradication therapy, and fexuprazan-based triple, quadruple, and dual regimens have shown promising efficacy and tolerability. Overall, current evidence indicates that fexuprazan is an effective and well-tolerated P-CAB that may overcome some of the limitations of conventional PPIs, while ongoing comparative and long-term studies will further define its place in the management of acid-related disorders. Medicines that reduce stomach acid are widely used to treat conditions such as heartburn, gastroesophageal reflux disease (GERD), and stomach infection caused by Helicobacter pylori. For many years, proton pump inhibitors (PPIs) have been the standard treatment, but they can take time to work, need to be taken before meals, and may not fully control acidity during the night. A newer class of drugs, called potassium-competitive acid blockers (P-CABs), has been developed to address some of these limitations. This review explains how one of these newer medicines, fexuprazan, works and summarizes current research on its effectiveness and safety. Studies show that fexuprazan can reduce stomach acid quickly and consistently, without being affected by food intake. In clinical trials, it healed esophageal damage from acid reflux as effectively as established treatments, with a trend for faster symptom relief and better night-time control. It may also help symptoms beyond typical heartburn, such as chronic cough or hoarseness. Early research suggests that fexuprazan could protect the lining of the digestive tract and improve treatment success for H. pylori infection. Overall, this medication may represent a flexible new option for managing acid-related diseases.