A request for additional stability data will delay the Food and Drug Administration (FDA)’s decision on the New Drug Application (NDA) for vonoprazan for the treatment of erosive esophagitis. The Agency was expected to take action on the application on or prior to January 11, 2023.

Vonoprazan, an oral small molecule potassium-competitive acid blocker, is currently under review for the healing of all grades of erosive esophagitis and relief of heartburn, and maintenance of healing of all grades of erosive esophagitis and relief of heartburn. The NDA is supported by data from the phase 3 PHALCON-EE trial (ClinicalTrials.gov Identifier: NCT04124926), which compared the efficacy and safety of vonoprazan to lansoprazole in 1024 patients with erosive esophagitis. 

Results showed that vonoprazan met its primary noninferiority endpoints in both the healing and maintenance phases and demonstrated superior maintenance of healing in all patients and patients with moderate to severe disease vs lansoprazole at week 24. Noninferiority was also demonstrated when vonoprazan was compared with lansoprazole in the mean percentage of 24-hour heartburn free days over both the healing and maintenance periods.

In August 2022, Phathom Pharmaceuticals announced that trace levels of the nitrosamine impurity, N-nitroso-vonoprazan (NVP), were detected in commercial batches. While the Company has worked closely with the FDA to establish an acceptable daily intake limit for NVP, the FDA is still requesting further stability data to ensure that the levels of NVP remain below the limit (<96ng/day) throughout the proposed shelf life of the product.

“While we are disappointed not to launch vonoprazan later this quarter, we are otherwise very pleased with the NDA review progress, including ongoing label negotiations which we are optimistic will conclude shortly,” said Terrie Curran, President and CEO of Phathom. “We are confident in our ability to meet the nitrosamine limit and expect to update anticipated launch timing after gaining further clarity on the stability requirements from the FDA.”

Reference

Phathom Pharmaceuticals provides update on New Drug Application review of vonoprazan for erosive esophagitis. News release. Phathom Pharmaceuticals. Accessed January 4, 2023. https://www.globenewswire.com/news-release/2023/01/03/2582483/0/en/Phathom-Pharmaceuticals-Provides-Update-on-New-Drug-Application-Review-of-Vonoprazan-for-Erosive-Esophagitis.html.