The novel potassium-competitive acid blocker is the first new treatment approved for the potentially cancer-producing GI disease in 30 years.
The FDA on Wednesday approved vonoprazan to treat adults with all grades of erosive esophagitis, also known as erosive gastroesophageal reflux disease (GERD). The novel potassium-competitive acid blocker, developed by Phatom Pharmaceuticals, is also indicated to maintain healing of all grades of erosive GERD and to relieve the associated heartburn, according to the company’s announcement.
The drug, to be marketed as Voquenza, is expected to be commercially available by December 2023.
“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, in the statement. “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.”
In addition to the discomfort of frequent heartburn, individuals with erosive GERD that is inadequately treated are at greater risk for Barrett’s esophagus, which in turn may predispose them to cancer. Erosive GERD affects approximately 20 million US adults.
The FDA based its approval on positive data from the pivotal phase 3 PHALCON-EE trial, a randomized, double-blind multicenter study that enrolled 1024 patients with erosive GERD in the United States and Europe. The study evaluated vonoprazan to the proton pump inhibitor (PPI) lansoprazole in its ability to heal and maintain healing of erosive GERD and to alleviate the associated heartburn.
The 20 mg strength of vonoprazan achieved the primary endpoint of non-inferiority (P < .001) for full healing by week 8 in patients with all grades of erosive GERD, demonstrating a healing rate of 93% compared with a rate of 85% observed for the 30 mg dose of lansoprazole.
The company also reported rates of healing with the 20-mg dose superior to those seen with lansoprazole 30 mg in a secondary endpoint in participants with moderate to severe disease at week 2 (70% vs 53%, respectively; P = .008).
Over the healing period vonoprazan 20 mg proved noninferior to lansoprazole 30 mg in the mean percentage of 24-hour heartburn-free days, according to the study findings. During the trial’s maintenance phase, vonoprazan 10 mg was more effective than lansoprazole 15 mg in continued healing at 6 months (79% v s 72% respectively). In a secondary endpoint, the 10 mg dose of vonoprazan was noninferior to lansoprazole 15 mg for heartburn relief over 6 months.
Overall adverse event (AE) rates were similar for the study and control drugs. In the healing phase those included gastritis, diarrhea, abdominal distension, abdominal pain, and nausea. Comparable rates for vonoprazan and lansoprazole during the maintenance phase were observed for abdominal pain, dyspepsia, hypertension, and urinary tract infection.
"The FDA approval of [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,” said Colin W. Howden, MD, professor emeritus of University of Tennessee College of Medicine, in the press release. “In addition, [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.”