FDA Issues Response Letter on Glepaglutide for Short Bowel Syndrome

Officials with the FDA issued Zealand Pharma a response letter saying that the application did not meet the full requirements for substantial evidence to establish the efficacy and safety of the to-be-marketed dose of glepaglutide for the treatment of short bowel syndrome in adults with intestinal failure.¹

The double-blind, phase 3 EASE-1 (NCT03690206) trial demonstrated that 24 weeks of treatment with 10 mg glepaglutide led to a drop in total weekly volume of parenteral support from baseline by 3.13 liters, but that reduction was not statistically significant with once-weekly doses and 5.13 liters (P=.0039) with twice-weekly doses compared with 2.85 liters with placebo.

Patients who received placebo in EASE-1 were rerandomized to treatment with either glepaglutide 10 mg once or twice weekly. Patients who complete EASE-2 are eligible to participate in EASE-3 (NCT04881825), evaluating glepaglutide administered once weekly using an auto-injector. EASE-4 (NCT04991311) is a phase 3b trial to assess long-term effects of glepaglutide on intestinal fluid and energy uptake.

Zealand Pharma expects to initiate a single phase 3 trial in 2025 that is anticipated to support marketing authorizations for glepaglutide in geographies outside the United States and European Union and provide further confirmatory evidence for a regulatory resubmission in the United States, according to a statement from the company.

Reference

1. Zealand Pharma. U.S. Food and Drug Administration issues Complete Response Letter for the glepaglutide New Drug Application for the treatment of short bowel syndrome. Press release. Published December 19, 2024. Accessed January 2, 2025. https://www.globenewswire.com/news-release/2024/12/19/3000220/0/en/U-S-Food-and-Drug-Administration-issues-Complete-Response-Letter-for-the-glepaglutide-New-Drug-Application-for-the-treatment-of-short-bowel-syndrome.html