Positive topline results from phase III PHALCON-NERD-301 trial evaluating daily dosing of vonoprazan for symptomatic non-erosive gastroesophageal reflux disease (NERD)- Phathom Pharma

Vonoprazan is an investigational first-in-class potassium-competitive acid blocker (PCAB) from a novel class of medicines that block acid secretion in the stomach. Full results from the study are expected later this year.

The topline results from the four-week, double-blind, placebo-controlled period showed both doses of vonoprazan 10 mg and 20 mg met the primary endpoint and demonstrated significantly greater percentage of 24-hour heartburn-free days versus placebo (mean 46.4% vonoprazan 10 mg, 46.0% vonoprazan 20 mg, compared to 27.5% for placebo; p<0.0001 for both vonoprazan 10 mg and 20 mg versus placebo). the median percentage of 24-hour heartburn-free days was 48.3%, 46.7% and 17.0% for vonoprazan 10 mg, vonoprazan 20 mg, and placebo, respectively.></0.0001>

“These data further demonstrate vonoprazan’s potential as a daily therapy in patients with NERD,” said Philip O. Katz, MD, Professor of Medicine and Director of Motility Laboratories at Weill Cornell Medicine, New York City. “NERD is a common cause of reflux-related symptoms and some patients with NERD fail to respond adequately to current therapies. As a practicing physician, I am excited about these data and the role this novel therapy may play in helping to address the needs of patients with symptomatic non-erosive gastroesophageal reflux disease.”

NERD is the largest subcategory of gastroesophageal reflux disease (GERD) and is characterized by reflux-related symptoms in the absence of esophageal mucosal erosions. There are estimated to be over 65 million individuals with GERD in the U.S., and it is estimated that 70% of this population have NERD.

The primary endpoint of the double-blind Phase III PHALCON-NERD-301 study evaluated the efficacy of vonoprazan 10 mg and 20 mg as a daily dosing (QD) treatment, as compared to placebo (QD), in the relief of heartburn over four weeks in participants with symptomatic NERD. The trial also includes a blinded 20-week long-term extension period, which is currently ongoing, to further evaluate the safety and efficacy of both doses of vonoprazan after six months of continuous use. A total of 776 patients with symptomatic NERD were enrolled and randomized in the multisite U.S. trial. Full results from the trial are expected to be presented later in 2023.

Vonoprazan was generally well tolerated in the initial four-week double-blind, placebo-controlled phase of the trial. The overall adverse events for all vonoprazan arms were comparable to placebo and consistent with what was reported in previous studies. The most commonly reported adverse event was nausea (2.3% vonoprazan 10 mg, 3.1% vonoprazan 20 mg, 0.4% placebo) with no other events reported above 3.0% in either vonoprazan dose arm. Full safety data from the study will be available following the completion of the 20-week long-term extension period.

“ The topline data are expected to form the basis of our FDA submission seeking approval of vonoprazan as a daily treatment for patients with NERD, following completion of the long-term extension portion of the trial,” said Terrie Curran, Phathom’s President and Chief Executive Officer. “These data are very encouraging for the treatment of NERD, a highly prevalent category of gastroesophageal reflux disease that causes disruptive day and nighttime symptoms for over 45 million patients in the U.S.”

Phathom is currently in discussions with the FDA on a separate Phase III trial design to evaluate the novel dosing regimen for vonoprazan as an on-demand or “as needed” treatment for episodic heartburn relief in patients with symptomatic NERD, a dosing treatment regimen not approved in the U.S. for proton pump inhibitors (PPIs). Positive results from Phathom’s Phase II PHALCON-NERD on-demand trial were previously presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting.