Topline Results Positive on Both Vonoprazan Doses for NERD

Nearly half of patients treated with vonoprazan 10 mg and 20 mg achieved more 24-hour heartburn free days compared to participants treated by placebo.

New topline data shows vonoprazan 10 mg and 20 mg doses results in a significantly greater percentage of 24-hour heartburn free days compared to placebo for patients with non-erosive gastroesophageal reflux disease (sGERD or NERD).

The results, announced by Phathom Pharmaceuticals, come from the four-week, double-blind, placebo-controlled phase 3 PHALCON-NERD-301 trial evaluating the efficacy and safety of vonoprazan for the daily treatment of 776 adults with symptomatic NERD.

The Trial

The results show both doses of the potassium-competitive acid blocker (PCAB) derived from a novel class of medicines that block acid secretion in the stomach met the primary endpoint and resulted a higher percentage of patients with heartburn free days compared to 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% in the vonoprazan 10 mg group, 46.7% in the vonoprazan 20 mg group, and just 17% in the placebo group.

The PHALCON-NERD-301 trial also included a blinded 20-week long-term extension period that is currently ongoing to further evaluate the safety and efficacy of both doses following 6 months of continuous use.

Safety

For safety, the treatment was generally well tolerated in the initial four-week phase of the trial. The rate of adverse events in all of the treatment arms was comparable to placebo and consistent with what was found in previous trials.

Nausea (2.3% vonoprazan 10 mg, 3.1% vonoprazan 20 mg, 0.4% placebo) was the most common adverse event reported, with no other adverse events above 3% in either vonoprazan dose arm.

“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, in a statement. “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). The disease is characterized by reflux-related symptoms with the absence of esophageal mucosal erosions. An estimated 65 million people have GERD in the US, 70% of which have NERD.

Phathom is expected to present the full set of data at some point in 2023. The company is also working with the US Food and Drug Administration (FDA) on another phase 3 trial evaluating a novel dosing regimen for the treatment as an on-demand or as needed treatment for episodic heartburn relief in patients with symptomatic NERD. The dosing regimen has not been approved by the FDA for proton pump inhibitors.