Zealand Pharma says FDA issues CRL for glepaglutide NDA

Zealand Pharma (ZLDPF) announced that the U.S. Food and Drug Administration has issued a Complete Response Letter for the company’s New Drug Application for glepaglutide, a long-acting GLP-2 analog, under development for the treatment of adult patients with short bowel syndrome with intestinal failure 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.