Vonoprazan improved nocturnal reflux symptoms in nonerosive disease, industry trial found

Vonoprazan was efficacious for nocturnal nonerosive reflux disease, an industry-funded trial found.

Vonoprazan is a potassium-competitive acid blocker that inhibits gastric acid secretion and was approved by the FDA in November 2023. To better understand the drug's effects on nighttime symptoms of gastroesophageal reflux disease, researchers conducted a prospective, randomized, double-blind, placebo-controlled phase 3 study at 91 U.S. centers. Included patients had a history of heartburn on four or more days in any consecutive seven-day period during screening, without esophagitis or Barrett's esophagus on endoscopy. Patients were randomized to placebo or to 10 mg or 20 mg of vonoprazan once daily for four weeks. For an extension period, patients receiving placebo were rerandomized to 10 mg or 20 mg of vonoprazan once daily.

The Nocturnal Gastro-esophageal Reflux Disease Symptom Severity and Impact Questionnaire (N-GSSIQ), a validated instrument for nocturnal gastroesophageal reflux disease, was completed at baseline and at weeks 4, 12, and 24. Minimal important differences for N-GSSIQ total score and subscales were defined as 0.4 or higher. A night was considered heartburn-free if the patient's completed morning diary entry indicated no heartburn or no use of rescue antacid, H2-receptor agonist, or proton pump-inhibitor. This study was sponsored by Phathom Pharmaceuticals, and the study authors reported that they were consultants or employees. Results were published Oct. 13 by the American Journal of Gastroenterology.

Among 772 patients, the mean percentage of heartburn-free nights at week 4 was 43.3% with placebo versus 59.9% with 10 mg of vonoprazan and 56.4% for 20 mg of vonoprazan (P<0.0001 for both comparisons). Both vonoprazan doses also improved N-GSSIQ total score (P<0.005 for both comparisons), nocturnal symptom severity subscale (P<0.001 for both comparisons), and concern about nocturnal reflux. The benefit on heartburn-free nights and N-GSSIQ scores with the drug continued for the rest of the study.

The study authors noted that the study was limited by lack of pH testing to document acid reflux as the cause of symptoms, meaning that some patients likely had conditions other than reflux. This may reduce the overall response rates seen with acid suppression, they wrote. The study included patients regardless of their prior medication use, different from other studies that required a history of at least partial responsiveness to acid-suppressive therapy, a broader inclusion criterion more closely reflecting a real-world clinical setting, the authors stated.