FDA approves vonoprazan for all grades of erosive GERD

The US Food and Drug Administration has approved a first-in-class oral potassium-competitive acid blocker vonoprazan (Voquezna) for all grades of erosive gastroesophageal reflux disease (GERD) and heartburn relief associated with the condition.Vonoprazan is first major innovation in erosive GERD in three decades, according to Phathom Pharmaceutical.

Erosive gastroesophageal reflux disease or erosive esophagitis is characterized by stubborn heartburn that without management can lead to Barrett's esophagus, a known precursor for esophageal cancer.

“This approval demonstrates Phathom's commitment to changing the GI treatment landscape for patients and healthcare providers, bringing the first major innovation to the U.S. Erosive GERD market in over 30 years,” said Terrie Curran, President and Chief Executive Officer at Phathom. “Erosive GERD can be extremely painful and often has a significant impact on patients. Research has shown patients and healthcare providers are largely unsatisfied with current treatments and we are excited about the approval of a first-in-class treatment option that has the potential to meet a large unmet medical need.”

Erosive GERD, also referred to as Erosive Esophagitis or Erosive Acid Reflux, is a major type of GERD that affects approximately 20 million people in the U.S.3,4 In addition to experiencing troubling heartburn symptoms, patients with inadequately treated Erosive GERD may develop more severe diseases including Barrett’s esophagus, a condition in which esophageal tissue changes can progress to cancer.3

This approval is based on positive results from the Phase 3 PHALCON-EE study (NCT04124926). The pivotal trial was a randomized, double-blind, multicenter study that enrolled 1,024 patients with Erosive GERD in the U.S. and Europe and compared VOQUEZNA to the PPI lansoprazole in the healing and maintenance of healing of Erosive GERD and associated heartburn symptom relief.1

Results showed that VOQUEZNA 20 mg met the primary endpoint of non-inferiority (p<0.0001) for complete healing by Week 8 in patients with all grades of Erosive GERD with a healing rate of 93% compared to 85% for lansoprazole 30 mg, with superior rates of healing demonstrated in a secondary endpoint in patients with moderate-to-severe disease (LA Grade C/D) at Week 2 compared to lansoprazole (70% for VOQUEZNA 20 mg and 53% for lansoprazole 30 mg) (p=0.0008). VOQUEZNA 20 mg also demonstrated non-inferiority to lansoprazole 30 mg in the mean percentage of 24-hour heartburn free days over the healing period. In the maintenance phase of the trial, VOQUEZNA 10 mg was superior to lansoprazole 15 mg in maintaining healing at six months in all randomized patients (79% for VOQUEZNA 10 mg, compared to 72% for lansoprazole 15 mg) as well as in the subset of patients with moderate-to-severe Erosive GERD (75% for VOQUEZNA 10 mg, compared to 61% for lansoprazole 15 mg) (p=0.0490). In addition, VOQUEZNA 10 mg was evaluated as a secondary endpoint for relief of heartburn in Erosive GERD patients and demonstrated non-inferiority to lansoprazole 15 mg over six months.

Adverse event (AE) rates for VOQUEZNA were comparable to lansoprazole in the trial. The most common AEs in the healing phase (≥ 2% in the VOQUEZNA treatment arm) were gastritis (3.0% for VOQUEZNA 20 mg and 2.0% for lansoprazole 30 mg), diarrhea (2.0% for VOQUEZNA 20 mg and 3.0% for lansoprazole 30 mg), abdominal distension (2.0% for VOQUEZNA 20 mg and 1.0 % for lansoprazole 30 mg), abdominal pain (2.0% for VOQUEZNA 20 mg and 1.0% for lansoprazole 30 mg) and nausea (2.0% for VOQUEZNA 20 mg and 1.0% for lansoprazole 30 mg). The most common AEs in the maintenance phase (≥ 3% in the VOQUEZNA treatment arm) for VOQUEZNA 10 mg compared to lansoprazole 15 mg were gastritis (6.0% vs. 3.0%), abdominal pain (4.0% vs. 2.0%), dyspepsia (4.0% vs. 3.0%), hypertension (3.0% vs. 2.0%), and urinary tract infection (3.0% vs. 2.0%). These are not all of the potential side effects associated with the use of VOQUEZNA. Please see Important Safety information below and the full Prescribing Information for VOQUEZNA for more information.

“For many GERD patients with Erosive Esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms5,” said Colin W. Howden, MD, Professor Emeritus, University of Tennessee College of Medicine. “The FDA approval of VOQUEZNA (vonoprazan) provides healthcare providers with a new first-in-class therapeutic option that demonstrated faster healing in the more difficult to treat GERD patients with Erosive Esophagitis. In addition, VOQUEZNA (vonoprazan) provided superior maintenance of healing in all grades of Erosive Esophagitis, compared to lansoprazole, a commonly prescribed PPI, and provided 24-hour heartburn relief on most days in the trial.”

VOQUEZNA is expected to be available in the U.S. in December 2023 and will be marketed exclusively by Phathom Pharmaceuticals, Inc.

Based on the terms of Phathom’s revenue interest financing agreement, the FDA approval of VOQUEZNA for Erosive GERD also entitles the company to receive a $175.0 million payment. This non-dilutive capital will help fund the commercial launch.