Phathom Pharmaceuticals has announced the publication of additional analyses from its pivotal Phase 3 pHalcon-NERD-301 trial, demonstrating that VOQUEZNA (vonoprazan) significantly improved nocturnal gastroesophageal reflux disease (GERD) symptoms in patients with Non-Erosive Reflux Disease (NERD). The results, published in the American Journal of Gastroenterology, highlight the potential of this first-in-class potassium-competitive acid blocker to address a challenging aspect of GERD management.
Addressing a Significant Clinical Need
Nighttime GERD symptoms represent a substantial clinical burden, affecting up to an estimated 80% of patients with GERD. These nocturnal symptoms can be associated with impaired sleep, reduced work productivity, and increased risk of esophageal and respiratory complications. Despite lifestyle interventions and widespread use of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs), many patients experience inadequate relief of nocturnal symptoms.
"Nocturnal symptoms can be among the most disruptive and difficult-to-manage aspects of GERD," said Philip Katz, MD, MACG, Professor of Medicine at Weill Cornell Medicine and study author. "This large, randomized trial provides important support for VOQUEZNA's potential role in improving sleep and daily functioning for patients with Non-Erosive Reflux Disease."
Trial Design and Patient Population
The Phase 3 pHalcon-NERD-301 trial randomized 772 patients to receive VOQUEZNA 10 mg, 20 mg, or placebo for an initial 4-week period. Patients receiving VOQUEZNA continued blinded active treatment for a 20-week extension, while those on placebo were re-randomized to VOQUEZNA 10 mg or 20 mg for the extension phase.
Key Efficacy Results
Heartburn-Free Nights
At week 4, patients receiving VOQUEZNA 10 mg and 20 mg achieved mean percentages of heartburn-free nights of 59.9% and 56.4%, respectively, compared to 43.3% for placebo (nominal p<0.0001, exploratory analysis not adjusted for multiple comparisons). The median percentages of heartburn-free nights during the 4-week placebo-controlled treatment period were 70.4% for VOQUEZNA 10 mg, 71.0% for VOQUEZNA 20 mg, and 45.5% for placebo.
Rapid Onset of Effect
The trial demonstrated rapid onset of therapeutic benefit, with separation from placebo observed after the first dose. Specifically, 45.3% of VOQUEZNA 10 mg and 52.4% of VOQUEZNA 20 mg patients experienced a heartburn-free night after the first dose versus 32.1% on placebo.
Patient-Reported Outcomes
Treatment with VOQUEZNA was associated with improvements from baseline versus placebo in total N-GSSIQ score (Nocturnal Gastroesophageal Reflux Disease Symptom Severity and Impact Questionnaire), and in the subscales of nocturnal symptom severity and concern about nocturnal GERD, but not on morning impact. These improvements were sustained through the 20-week extension treatment period.
Durability of Response
VOQUEZNA demonstrated sustained nocturnal symptom relief throughout the full treatment period, consistent with the 24-hour heartburn relief observed in the full pHalcon-NERD-301 trial. Median heartburn-free nights remained above 70% across all treatment groups through the 20-week active extension.
Safety Profile
VOQUEZNA was generally well tolerated in both phases of the trial. The most common adverse events (≥3%) in the 4-week period were nausea, abdominal pain, constipation, diarrhea, and urinary tract infection. In the 20-week extension, the most common adverse events (≥5%) included upper respiratory tract infection, sinusitis, influenza, urinary tract infection, nasopharyngitis, nausea, and gastroenteritis.
Clinical Significance
"The publication of these data in The American Journal of Gastroenterology adds to the growing body of clinical evidence evaluating VOQUEZNA as a novel potassium-competitive acid blocker with the potential to address the unmet needs for patients with GERD, including those with bothersome nighttime symptoms who often have been inadequately managed by existing therapies," said Eckhard Leifke, MD, Chief Medical Officer at Phathom.
Disease Context
Non-Erosive GERD is the largest subcategory of gastroesophageal reflux disease and is characterized by reflux-related symptoms in the absence of esophageal mucosal erosions. There are an estimated 38 million U.S. adults living with Non-Erosive GERD, of which approximately 15 million are treated with a prescription medicine annually. Symptoms can impact overall quality of life and may include episodic heartburn, especially at night, regurgitation, problems swallowing, and chest pain.
About VOQUEZNA
VOQUEZNA (vonoprazan) tablets contain vonoprazan, an oral small molecule potassium-competitive acid blocker (PCAB). PCABs represent a novel class of medicines that block acid secretion in the stomach. VOQUEZNA is approved in the U.S. for the treatment of adults with Erosive Esophagitis, the relief of heartburn associated with Erosive GERD, the relief of heartburn associated with Non-Erosive GERD, and for the treatment of H. pylori infection in combination with either amoxicillin or amoxicillin and clarithromycin. Phathom in-licensed the U.S. rights to vonoprazan from Takeda, which markets the product in Japan and numerous other countries in Asia and Latin America.
