Zealand Pharma submits New Drug Application to the US FDA for glepaglutide in short bowel syndrome

Press release – No. 18 / 2023

Zealand Pharma submits New Drug Application to the US FDA for glepaglutide in short bowel syndrome

Copenhagen, Denmark, December 22, 2023 – 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 the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for glepaglutide, a long-acting GLP-2 analog, for the treatment of adult patients with short bowel syndrome (SBS) dependent on parenteral support.

“Short bowel syndrome with intestinal failure is a complex, chronic and severe condition 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. More effective and convenient treatments to further reduce parenteral support are needed, with the ultimate goal of discontinuing parenteral support and achieving enteral autonomy,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “We believe glepaglutide, once approved, can reduce both the burden of parenteral support and of daily dosing of existing GLP-2 treatment for people living with SBS and intestinal failure, and we are pleased to submit this treatment for regulatory review and potential approval in the US.”

About EASE Clinical Trial Program

The submission is based on the results from a pivotal Phase 3 trial (EASE-1), supported by interim results from two ongoing long-term extension trials (EASE-2 and EASE-3), and a mechanistic trial (EASE-4).

EASE-1 (NCT03690206) was a randomized, double-blind Phase 3 trial that evaluated the safety and efficacy of once- and twice-weekly subcutaneous administration of glepaglutide 10 mg compared to placebo in 106 SBS patients with intestinal failure who were dependent on parenteral support (PS) at least three days per week. Glepaglutide given twice weekly significantly reduced the total weekly volume of PS at 24 weeks as compared to placebo (p=0.0039) in this trial. When administered once weekly, glepaglutide treatment also resulted in a numeric reduction in weekly PS, however this did not achieve statistical significance. At 24 weeks, the average reduction in PS from baseline was 5.13 liters/week for patients treated with glepaglutide twice weekly and was 3.13 liters/week for patients treated with glepaglutide once weekly. Placebo treatment resulted in a reduction in PS of 2.85 liters/week. A total of 9 patients treated with glepaglutide were completely weaned off PS (enteral autonomy), while no placebo-treated patients were able to discontinue PS. For patients treated with glepaglutide twice-weekly, 14% of patients (n=5) achieved enteral autonomy.

Patients who completed EASE-1 could enroll in the extension trials, EASE-2 and subsequently EASE-3, designed to assess long-term safety and efficacy of glepaglutide.

EASE-2 (NCT03905707) is a randomized, double-blind trial in which SBS patients continued their randomly 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. In an interim analysis conducted when all patients had completed at least six months of treatment, clinical response to glepaglutide across the key efficacy endpoints was generally maintained or showed continued improvement, including additional patients on both doses weaning off PS.

EASE-3 (NCT04881825) is evaluating glepaglutide administered once weekly using an auto-injector. An interim analysis of EASE-3, conducted with the first 43 patients rolled over from EASE 2, showed that the reduction in prescribed PS was generally maintained.

EASE-4 (NCT04991311) is a Phase 3b trial to assess mechanistic effects of glepaglutide on intestinal fluid and energy uptake.

Glepaglutide appeared to be safe and was well-tolerated in all trials. The most frequently reported adverse events were injection site reactions and gastrointestinal events.

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 by twice weekly dosing, 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 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 blue-chip pharma companies as well as commercial partnerships for its marketed products.

Founded in 1998 and headquartered in Copenhagen, Denmark, Zealand has a team in the U.S. For more information about Zealand’s business and activities, please visit http://www.zealandpharma.com.

Forward-Looking Statements
This press release contains forward-looking statements that provide Zealand Pharma’s expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products. 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, the occurrence of adverse safety events; risks of unexpected costs or delays; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; 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 fail to approve or may delay approval of our drug candidates or expansion of product labelling; failure to obtain regulatory approvals in other jurisdictions; and product liability claims. 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 company announcement and are based on information available to Zealand Pharma as of the date of this 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.

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