Copenhagen, Denmark – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company transforming the future of metabolic health, today announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending marketing authorization for Zeydovio™ (glepaglutide), a long-acting, next-generation GLP-2 analog, for the treatment of adults with short bowel syndrome (SBS).
“The positive opinion for Zeydovio™ is the first major advancement in short bowel syndrome treatment in Europe in more than a decade. Those living with short bowel syndrome face significant daily burdens and are susceptible to significant health risks from parenteral support, and every day free from it can be life changing. In the Phase 3 trials, Zeydovio™ significantly reduced parenteral support volume, reducing the number of days required for many patients and eliminating the need for it entirely in others,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “Offering simple dosing twice weekly via a ready-to-use autoinjector, Zeydovio™ holds potential as a transformative therapy for SBS that could meaningfully ease the burden of disease management for thousands of patients.”
The positive opinion is based on data from the pivotal Phase 3 EASE-1 trial, in which twice-weekly glepaglutide demonstrated statistically significant and superior reductions in parenteral support requirements in SBS patients with intestinal failure (IF) compared to placebo. These data were supported by interim results from the EASE-2 and EASE-3 trials, the long-term extension trials of up to two years, and results from a mechanistic trial (EASE-4) providing evidence of glepaglutide’s pharmacodynamic effects in improving intestinal absorption. In the clinical trials to date, glepaglutide treatment appeared safe and well tolerated. Results from the EASE-2 and EASE-3 trials, which confirmed the long-term efficacy and safety of glepagutide, are expected to be presented at scientific meetings in 2027.
The CHMP’s opinion will now be reviewed by the European Commission, with a final decision on the Marketing Authorization Application (MAA) expected within approximately 67 days. Subject to European Commission approval, the marketing authorization would be valid in all member states of the European Union, as well as Iceland, Liechtenstein, and Norway.
Zealand Pharma is actively engaging in partnership discussions for the future global commercialization of glepaglutide for SBS.
The Phase 3 EASE-5 trial, designed to provide further confirmatory evidence to support a regulatory submission in the U.S., is ongoing, with patient recruitment progressing well.
About short bowel syndrome
Short bowel syndrome (SBS) is a rare, chronic and severe disease associated with reduced or complete loss of intestinal function, leaving many patients chronically dependent on complex parenteral support (PS). While life-sustaining, parenteral support poses significant restrictions on patients’ ability to engage in daily activities. In addition, they are at risk of experiencing a number of serious and life-threatening complications such as sepsis, blood clots, liver damage and renal impairment.
About glepaglutide
Glepaglutide is a long-acting GLP-2 analog in development for the treatment of short bowel syndrome, aiming to reduce or eliminate the need for parenteral support by improving intestinal function. With its long half-life and high stability in aqueous solution, glepaglutide is developed for twice-weekly, subcutaneous administration via a ready-to-use, single-dose autoinjector. The U.S. FDA has granted orphan drug designation for glepaglutide for the treatment of SBS.
About the EASE Clinical Trial Program
The Phase 3 program, named EASE, is designed to evaluate the potential for glepaglutide to reduce or eliminate the need for PS in SBS patients with intestinal failure.
EASE-1 (NCT03690206) was a randomized, double-blind Phase 3 trial in 106 SBS patients with intestinal failure who were dependent on PS for at least three days per week. Patients were evenly randomized to receive glepaglutide 10 mg once or twice weekly, or placebo. The primary endpoint was the absolute change in weekly PS volume from baseline at 24 weeks. At 24 weeks, glepaglutide administered twice weekly significantly reduced the total weekly volume of PS by 5.13 liters/week compared to 2.85 liters/week in the placebo group (p=0.0039). Clinical efficacy was observed in patients with and without colon-in-continuity. Among patients receiving glepaglutide twice weekly, 65.7% achieved a clinical response, defined as at least 20% reduction in weekly PS volume at 24 weeks (versus 38.9% in the placebo group), and 51.4% of patients achieved a reduction in PS days of at least 1 day/week (versus 19.4% in the placebo group). Nine patients treated with glepaglutide were completely weaned off PS (achieving enteral autonomy), while no placebo-treated patients achieved enteral autonomy. For patients treated twice weekly, 14% (n=5) achieved enteral autonomy. Glepaglutide treatment appeared safe and well tolerated.
In total, 102 of 106 participating patients completed EASE-1, of which 96 continued into the two-year long-term safety and efficacy extension trial, EASE-2.
EASE-2 (NCT03905707) was 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 glepaglutide 10 mg once- or twice-weekly. In addition, a smaller group of patients not previously treated with glepaglutide were directly randomized to receive glepaglutide 10 mg once- or twice weekly. In an interim analysis after at least six months of treatment, clinical response across the key efficacy endpoints was generally maintained or showed continued improvement, including additional patients on both doses weaning off PS.
Patients who completed EASE-2 were eligible for EASE-3 (NCT04881825), evaluating glepaglutide administered once weekly using an autoinjector. The EASE-2 and EASE-3 trials were completed in 2026, and the remaining patients have rolled over to a new extension trial, EASE-6 (NCT07228403). Results from the EASE-2 and EASE-3 trials are expected to be presented at scientific meetings in 2027.
EASE-4 (NCT04991311) was a Phase 3b trial to assess mechanistic effects of glepaglutide once weekly on intestinal fluid and energy uptake, providing evidence of the pharmacodynamic effects of glepaglutide in improving intestinal absorption. The primary endpoint was absolute change in intestinal wet weight absorption. Secondary endpoints assessed changes in energy, electrolyte, and macronutrient absorption after 24 weeks of treatment. Additional endpoints included changes in PS use, body composition and safety after 52 weeks of treatment. At week 24, mean numerical increase in intestinal wet weight absorption was 398 g/day (p=0.0585) and mean energy absorption 1038 kJ/day (p=0.0215). Improvements occurred in electrolyte and macronutrient absorption. At week 52, mean PS volume was reduced by 800 mL/day (p=0.0106) with a reduction in mean PS energy content of 866 kJ/day (p=0.0103).
EASE-5 (NCT07197944) is a randomized, double-blind, placebo-controlled Phase 3 trial, designed to confirm the efficacy and safety of glepaglutide twice weekly, followed by a long-term, open-label safety evaluation in SBS patients with intestinal failure.
About Zealand Pharma A/S
Zealand Pharma A/S (Nasdaq: ZEAL) is a biotechnology company focused on advancing medicines for obesity and metabolic health. Combining more than 25 years of peptide R&D expertise with a proprietary data platform that leverages advanced data‑driven and AI/ML approaches, Zealand Pharma aims to lead a new era in obesity and metabolic health.
To date, more than ten Zealand Pharma‑invented drug candidates have entered clinical development, of which two products have reached the market and three candidates are in late-stage development. The Company has collaborations with global pharmaceutical and biotechnology partners for research, development, and commercialization.
Founded in 1998, Zealand Pharma is headquartered in Copenhagen, Denmark, with a U.S. presence in Boston, Massachusetts. Learn more at www.zealandpharma.com.
Zealand Pharma® is a registered trademark of Zealand Pharma A/S.
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