The New Drug Application for vonoprazan for the treatment of erosive esophagitis has been submitted to the Food and Drug Administration (FDA).
Vonoprazan is an oral small molecule potassium-competitive acid blocker. The application is supported by data from the double-blind 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.
In the first phase of the trial, patients were randomly assigned to receive vonoprazan 20mg orally once daily or lansoprazole 30mg orally once daily for up to 8 weeks. Patients who achieved complete healing entered the maintenance phase, and were randomly assigned to receive vonoprazan 10mg or 20mg orally once daily or lansoprazole 15mg orally once daily for up to 24 weeks.
Results from the first phase showed that vonoprazan was associated with a healing rate of 93% compared with 85% for lansoprazole (P <.0001), demonstrating noninferiority of the investigational treatment (primary endpoint). The difference in healing rate was also found to be statistically significant in an exploratory superiority test (P <.0001). Additionally, significantly faster healing (at week 2) was observed in patients with moderate to severe disease treated with vonoprazan vs lansoprazole (secondary endpoint; P =.0004)
In the maintenance phase, both doses of vonoprazan were found to be noninferior to lansoprazole, with 79% and 81% of patients treated with the 10mg and 20mg dose, respectively, maintaining complete healing of erosive esophagitis through 24 weeks vs 72% of patients in the lansoprazole group (primary endpoint). Moreover, the percentage of patients with moderate to severe disease who maintained healing of erosive esophagitis was observed to be greater with vonoprazan 10mg (75%) and vonoprazan 20mg (77%) vs lansoprazole (61%).
Noninferiority was also observed when vonoprazan was compared with lansoprazole in the mean percentage of 24-hour heartburn free days over both the healing and maintenance periods.
“Today’s results indicate an advancement in the treatment of erosive esophagitis,” said Loren Laine, MD, Professor of Medicine and Chief, Digestive Diseases at Yale School of Medicine, and lead investigator of the PHALCON-EE study. “The PHALCON-EE data support vonoprazan as a novel potential alternative to [proton pump inhibitors] to improve healing and reduce recurrence of erosions in patients with erosive esophagitis.”
Phathom Pharmaceuticals is also seeking approval of vonoprazan in combination with antibiotics for the treatment of Helicobacter pylori (H. pylori) infection in adults.
- Phathom Pharmaceuticals submits vonoprazan NDA to FDA for the treatment of erosive esophagitis. News release. Phathom Pharmaceuticals. Accessed March 14, 2022. https://www.globenewswire.com/news-release/2022/03/14/2402533/0/en/Phathom-Pharmaceuticals-Submits-Vonoprazan-NDA-to-FDA-for-the-Treatment-of-Erosive-Esophagitis.html
- Phathom Pharmaceuticals announces positive topline results from PHALCON-EE pivotal phase 3 erosive esophagitis trial. News release. Phathom Pharmaceuticals. October 18, 2021. Accessed March 14, 2022. https://investors.phathompharma.com/news-releases/news-release-details/phathom-pharmaceuticals-announces-positive-topline-results-0