Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial

Abstract

Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in U.S. subjects diagnosed with non-erosive reflux disease (NERD) of vonoprazan vs. placebo for 4 weeks followed by a 20-week active-treatment extension. Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10mg, or vonoprazan 20mg. After 4 weeks, subjects on placebo were re-randomized to vonoprazan 10 or 20mg and those already on vonoprazan continued at the same dose for 20 weeks. Electronic diaries were completed twice daily. The primary endpoint was percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days). Among 772 randomized subjects, the percentage of 24-hour heartburn-free days was 27.7% for placebo vs. 44.8% for vonoprazan 10mg (least squares mean difference=17.1%, p<0.0001) and 44.4% for vonoprazan 20mg (least squares mean difference=16.7%, p<0.0001). Differences in percentage of subjects with a 24-hour heartburn-free day for vonoprazan 10mg vs. placebo and vonoprazan 20mg vs. placebo were 8.3% and 11.6% on day 1 and 18.1% and 23.2% on day 2. The mean/median percentages of 24-hour heartburn-free days over the extension period were similar across the four study arms: 61-63%/76-79%. Vonoprazan reduced heartburn symptoms in subjects diagnosed with NERD, with the benefit appearing to begin as early as the first day of therapy. Treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period. The two vonoprazan doses (10 and 20mg) were similar in efficacy. (ClinicalTrials.gov:NCT05195528).