U.S. Food and Drug Administration issues Complete Response Letter for the glepaglutide New Drug Application for the treatment of short bowel syndrome

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.

About short bowel syndrome

Short bowel syndrome (SBS) with intestinal failure is a complex chronic and severe condition associated with reduced or complete loss of intestinal function in which individuals are dependent on receiving fluids and nutrition parenterally. While life-sustaining, parenteral support poses significant restrictions on daily life and carries a risk of serious and life-threatening complications such as sepsis, blood clots, liver damage and renal impairment.

About Zealand Pharma A/S 

Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products.

Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand’s business and activities, please visit www.zealandpharma.com.

Forward-Looking Statements
This company announcement contains "forward-looking statements”, as that term is defined in the Private Securities Litigation Reform Act of 1995 in the United States, as amended, even though no longer listed in the United States this is used as a definition to provide Zealand Pharma’s expectations or forecasts of future events regarding the research, development, and commercialization of pharmaceutical products, the timing of the company’s clinical trials and the reporting of data therefrom. These forward-looking statements may be identified by words such as "aim,” "anticipate,” "believe,” "could,” "estimate,” "expect,” "forecast,” "goal,” "intend,” "may,” "plan,” "possible,” "potential,” "will,” "would”, and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented. The reader is cautioned not to rely on these forward-looking statements. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions, which may cause actual results to differ materially from expectations set forth herein and may cause any or all of such forward-looking statements to be incorrect, and which include, but are not limited to, unexpected costs or delays in clinical trials and other development activities due to adverse safety events or otherwise; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; our ability to successfully market both new and existing products; changes in reimbursement rules and governmental laws and related interpretation thereof; government-mandated or market-driven price decreases for our products; introduction of competing products; production problems; unexpected growth in costs and expenses; our ability to effect the strategic reorganization of our businesses in the manner planned; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies, or may reject, fail to approve or may delay approval of our drug candidates or expansion of product labeling; failure to obtain regulatory approvals in other jurisdictions; exposure to product liability and other claims; interest rate and currency exchange rate fluctuations; unexpected contract breaches or terminations; inflationary pressures on the global economy; and political uncertainty, including due to the ongoing military conflict in Ukraine. If any or all of such forward-looking statements prove to be incorrect, our actual results could differ materially and adversely from those anticipated or implied by such statements. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. All such forward-looking statements speak only as of the date of this press release/company announcement and are based on information available to Zealand Pharma as of the date of this release/announcement. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

Contacts

Neshat Ahmadi (Investors)
Investor Relations Manager
Email: neahmadi@zealandpharma.com

Adam Lange (Investors)
Investor Relations Officer
Email: alange@zealandpharma.com

Anna Krassowska, PhD (Media and Investors)
Vice President, Investor Relations & Corporate Communications
Email: akrassowska@zealandpharma.com