Company announcement - No. 51 / 2024
U.S. Food and Drug Administration issues Complete Response Letter for the glepaglutide New Drug Application for the treatment of short bowel syndrome
The FDA concluded that Zealand Pharma's application did not meet the full requirements for substantial evidence to establish the efficacy and safety of the to-be-marketed dose of glepaglutide.
Zealand Pharma will continue the dialogue with the FDA to align on the path toward obtaining regulatory approval in the U.S.
Zealand Pharma expects to proceed with its current plans for a European Marketing Authorization Application submission in 2025.
Copenhagen, Denmark, December 19, 2024 - Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the company's New Drug Application (NDA) for glepaglutide, a long-acting GLP-2 analog, under development for the treatment of adult patients with short bowel syndrome (SBS) with intestinal failure (IF) who are dependent on parenteral support.
The submitted NDA included a single randomized, placebo-controlled Phase 3 registration trial, which is common for a rare disease indication such as SBS. The trial consisted of two active treatment arms, a once-weekly and twice-weekly dosing arm, respectively. Treatment with glepaglutide twice-weekly demonstrated significant and superior effects in reducing parenteral support requirements in patients with SBS-IF compared to placebo. Once-weekly glepaglutide treatment resulted in a reduction in parenteral support, but did not achieve statistical significance. In the CRL, the FDA recommended an additional clinical trial to provide further evidence to confirm the efficacy and safety of glepaglutide at the to-be-marketed dose.
"While we are certainly disappointed in the FDA's decision, we remain confident that the data showed robust and compelling evidence of both efficacy and safety for glepaglutide treatment. We remain firm in our belief that glepaglutide provides a significant advance in GLP-2-based therapies for the potential treatment of SBS patients who are dependent on parenteral support," said David Kendall, MD, Chief Medical Officer of Zealand Pharma. "We are committed to working with the agency to align on the path toward a regulatory approval, so that we can bring glepaglutide to patients in the U.S. In parallel, we expect to proceed with our current plans for a European Marketing Authorization Application submission in 2025."
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 U.S. and the EU and provide further confirmatory evidence for a regulatory resubmission in the U.S.
About glepaglutide
Glepaglutide is a long-acting GLP-2 analog in development as a potential treatment option for short bowel syndrome (SBS). Glepaglutide is being developed as a liquid product in an autoinjector designed for subcutaneous administration, aimed to reduce, or eliminate, the need for parenteral support in people living with SBS. The U.S. Food and Drug Administration (FDA) has granted orphan drug designation for glepaglutide for the treatment of SBS.
About the EASE clinical program
The Phase 3 program, named EASE, includes four clinical trials evaluating the potential for glepaglutide to reduce or eliminate the need for parenteral support in SBS patients with intestinal failure.
EASE-1 (NCT03690206) is a randomized, double-blind Phase 3 trial that enrolled a total of 106 SBS patients with intestinal failure who were dependent on parenteral support for at least three days per week. Patients were evenly randomized to receive treatment with 10 mg glepaglutide administered either once or twice weekly, or placebo. The primary endpoint in the trial was the absolute change in weekly parenteral support volume from baseline at 24 weeks.
In total, 102 of 106 participating patients completed EASE-1, of which 96 continued into the ongoing two-year, long-term safety and efficacy extension trial, EASE-2. EASE-2 (NCT03905707) is a randomized, double-blind trial in which SBS patients continued their assigned treatment from EASE-1 with glepaglutide 10 mg once or twice weekly. Patients who received placebo in EASE-1 were re-randomized 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.
