Novel Acid Blocker Shows Promise for Non-Erosive Reflux Disease

A recent phase III clinical trial indicates that once-daily oral administration of tegoprazan, a novel potassium-competitive acid blocker, significantly decreases heartburn frequency in individuals diagnosed with non-erosive reflux disease. The findings were presented by Ronnie Fass, MD, of the Case Western Reserve University School of Medicine, at the annual meeting of the American College of Gastroenterology in Nashville, Tennessee.

Understanding Non-Erosive Reflux Disease

Gastroesophageal reflux disease affects up to 20% of adults in the United States, and non-erosive reflux disease represents its most common phenotype, impacting up to 70% of those patients. Standard treatment often involves proton pump inhibitors. However, approximately 35% of patients report dissatisfaction with those therapies, noting that symptom relief with standard-dose proton pump inhibitors hovers around 50%.

Potassium-competitive acid blockers and proton pump inhibitors both function by inhibiting the proton pump, but they exhibit distinct pharmacokinetics and pharmacodynamics. Researchers noted that tegoprazan features a structural profile and unique binding properties that allow for a rapid onset of action, achieving a stomach pH level above 4 within 45 minutes of administration.

Phase III Trial Design and Results

The double-blind study, known as the TRIUMpH-NERD trial, was conducted across 91 sites in the United States and enrolled 783 patients. Participants were required to have documented heartburn symptoms for a minimum of six months before randomization, a normal endoscopy during a one-week screening period, and at least four days of heartburn symptoms during that same timeframe.

Participants were randomized to receive either a placebo, 50 mg of tegoprazan, or 100 mg of tegoprazan. Through four weeks of treatment, the mean percentages of 24-hour heartburn-free days were:

• 17.3% for the placebo group
• 26.2% for the 50-mg tegoprazan group
• 30.1% for the 100-mg tegoprazan group

These figures translate to relative improvements of 51% and 74% with the 50-mg and 100-mg doses of tegoprazan compared to placebo. Secondary endpoints evaluating percentages of days without daytime and nighttime heartburn also favored the treatment arms. Furthermore, an exploratory endpoint demonstrated that tegoprazan significantly improved the percentage of regurgitation-free days compared with placebo.

Important Considerations and Limitations

During the meeting Q and A session, investigators addressed questions regarding improvements observed in the placebo arm over time, noting that lifestyle modifications and a standard placebo response can occur in clinical evaluations. Nevertheless, researchers emphasized that a clear separation in efficacy remained between the active treatment arms and the placebo group.

Regarding safety, the rates of serious treatment-emergent adverse events were comparable across all study arms. Treatment-emergent adverse events leading to discontinuation occurred in 1.1% of the placebo group, 1.9% of the 50-mg tegoprazan group, and 1.5% of the 100-mg tegoprazan group. A new drug application for tegoprazan in the treatment of gastroesophageal reflux disease was submitted to the Food and Drug Administration earlier in the year.