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The FDA approved vonoprazan (Voquezna) for all grades of erosive gastroesophageal reflux disease (GERD) and heartburn relief associated with the condition, on Wednesday.

Vonoprazan, a first-in-class oral potassium-competitive acid blocker (PCAB), represents the "first major innovation" in erosive GERD in three decades, according to the company. The condition, also know as erosive esophagitis or erosive acid reflux, is characterized by stubborn heartburn that without management can lead to Barrett's esophagus, a recognized precursor for esophageal cancer.

Phase III data from the PHALCON-EE study supported the approval. In that double-blind trial, which randomized over 1,000 patients with all grades of erosive GERD in the U.S. and abroad, PCAB demonstrated noninferiority when it came to healing and superiority for maintaining healing versus the proton pump inhibitor (PPI) lansoprazole (Prevacid).

"For many GERD patients with erosive esophagitis, the response to current treatment is suboptimal, leaving them with incomplete healing and ongoing symptoms," Colin Howden, MD, of the University of Tennessee College of Medicine in Memphis, said in a statement. "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."

At 8 weeks in the study, complete healing rates across all grades reached 93% with a 20-mg dose of vonoprazan versus 85% with a 30-mg dose of lansoprazole (P<0.0001 for noninferiority), and the patients on vonoprazan had more heartburn-free days during this healing part of the trial. At 2 weeks, vonoprazan also showed significantly superior healing rates for the subset of patients with moderate-to-severe disease, as determined by the Los Angeles Classification system (70% vs 53%, P=0.0008).

In addition, the drug "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," said Howden, who served as an investigator on vonoprazan studies in Helicobacter pylori infections, where the drug is also approved in combination with antibiotics.

During maintenance, lower doses of the drugs were used (10 mg for vonoprazan and 15 mg for lansoprazole). Here the PCAB proved superior to lansoprazole at 6 months across all disease grades, with 79% of participants assigned to vonoprazan maintaining healing versus 72% of those randomized to lansoprazole. The moderate-to-severe subset experienced an even larger between-group difference (75% vs 61%, respectively, P=0.049).

Similar rates of adverse events (AEs) in PHALCON-EE were observed between drugs, according to the drugmaker. cites common AEs during the 8-week healing phase of gastritis (3%), diarrhea (2%), abdominal distension (2%), abdominal pain (2%), and nausea (2%). During maintenance, the most common AEs with PCAB include gastritis (6%), abdominal pain (4%), dyspepsia (4%), hypertension (3%), and urinary tract infections (3%).

The drug is contraindicated with rilpivirine-containing regimens used for treating HIV. Other warnings and precautions include that response to vonoprazan does not preclude gastric malignancy, potential risks for Clostridioides difficile-associated diarrhea and bone fractures, and that long-term use of the drug may increase the risk for fundic gland polyps and vitamin B12 deficiency. The drug should be discontinued in patients who develop acute tubulointerstitial nephritis or have severe cutaneous adverse reactions following treatment.

Vonoprazan, which comes in 10 mg and 20 mg tablets, is expected to be available in December, said Phathom. The recommended dosage is 20 mg once-daily during the 8-week healing phase and 10 mg once-daily during the 6-month maintenance period.

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