Zeydovio (glepaglutide) / Zealand Pharma - LARVOL DELTA

Zealand Pharma A/S…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)…for the treatment of adults with short bowel syndrome (SBS) (GlobeNewswire) - "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....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."

CHMP • P3 data • Short Bowel Syndrome

EASE SBS 2: Evaluation of Long Term Safety and Efficacy of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=150 | Completed | Sponsor: Zealand Pharma | Active, not recruiting ➔ Completed

Trial completion • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 3: Evaluation of Long Term Safety and Efficacy of Glepaglutide in Treatment of SBS - Extension Trial (clinicaltrials.gov) - P3 | N=84 | Completed | Sponsor: Zealand Pharma | Active, not recruiting ➔ Completed | N=129 ➔ 84

Enrollment change • Trial completion • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 6: Efficacy and Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (clinicaltrials.gov) - P3 | N=28 | Active, not recruiting | Sponsor: Zealand Pharma | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Disorder • Short Bowel Syndrome

Beyond intestinal failure: Expanding therapeutic frontiers of glucagon-like peptide-2 in gastrointestinal disease. (PubMed, World J Gastrointest Pharmacol Ther) - "Clinical trials have demonstrated that teduglutide and newer long-acting analogues such as glepaglutide significantly increase plasma citrulline levels, reduce fecal output, and decrease PN requirements while improving hepatic function and quality of life. GLP-2 analogues represent a paradigm shift in short bowel syndrome management, transforming care from supportive nutrition to regenerative therapy. Ongoing studies exploring novel formulations, broader indications, and precision medicine approaches will further refine their clinical integration and maximize therapeutic benefit."

Journal • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Short Bowel Syndrome • IGF1

EASE SBS 6: Efficacy and Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (clinicaltrials.gov) - P3 | N=35 | Enrolling by invitation | Sponsor: Zealand Pharma

Trial initiation date • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 5: Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=90 | Recruiting | Sponsor: Zealand Pharma

Trial initiation date • Gastrointestinal Disorder • Short Bowel Syndrome

Glepaglutide in SBS (GlobeNewswire) - "Zealand Pharma expects potential regulatory approval in the EU in the first half of 2026."

EMA approval • Short Bowel Syndrome

EASE SBS 5: Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=90 | Recruiting | Sponsor: Zealand Pharma

Trial initiation date • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 5: Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=90 | Recruiting | Sponsor: Zealand Pharma

Trial initiation date • Gastrointestinal Disorder • Short Bowel Syndrome

Glucagon-like peptide agonists and use in short bowel syndrome - what about the side effects? (PubMed, Curr Opin Gastroenterol) - "While GLP-2 agonists shape the current landscape of SBS management, GLP-1 based therapies may complement future treatment strategies offering the potential to reduce or even eliminate dependence on PS. Continued long-term studies and registry data are essential to optimize patient selection, safety monitoring, and personalized use of GLP agonists."

Adverse events • Journal • Gastrointestinal Disorder • Short Bowel Syndrome

Exploring the disease burden and quality of life in patients with short bowel syndrome with intestinal failure: Insights from exit interviews in the glepaglutide EASE SBS-1 phase 3 trial. (PubMed, Nutr Clin Pract) - "During exit interviews, patients receiving glepaglutide reported improvements in well-being across multiple domains, noting meaningful reductions in PS volume and a reduced impact of SBS-IF on daily life, which was proportionally greater than in those receiving placebo. These findings underscore the patient-reported positive experiences of glepaglutide and its beneficial effects."

Clinical • HEOR • Interview • Journal • P3 data • Gastrointestinal Disorder • Pain • Short Bowel Syndrome • Sleep Disorder

ZP1848-25009: A trial to assess the long-term safety and effectiveness of glepaglutide in patients with short bowel syndrome who have been previously treated with the medicine (clinicaltrialsregister.eu) - P2/3 | N=19 | Active, not recruiting | Sponsor: Zealand Pharma A/S

New P2/3 trial • Gastrointestinal Disorder • Short Bowel Syndrome

ZP1848-23029: EASE SBS 5 (Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS) (clinicaltrialsregister.eu) - P2/3 | N=72 | Recruiting | Sponsor: Zealand Pharma A/S

New P2/3 trial • Gastrointestinal Disorder • Short Bowel Syndrome

Investigation of the stool microbiome of Short Bowel Syndrome patients before and after a 24-week treatment with the Glucagon-like Peptide 2 analog glepaglutide. (PubMed, Clin Nutr ESPEN) - P3 | "Treatment with the GLP-2 analog glepaglutide increased intestinal wet weight and energy absorption without altering the intestinal bacterial microbiota in the majority of the SBS patients participating in this study. Differences in bacterial load and composition were influenced by intestinal anatomy."

Journal • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 5: Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=90 | Recruiting | Sponsor: Zealand Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Disorder • Short Bowel Syndrome

Letter to the editor: Interpreting pooled GLP-2 analogue effects in chronic intestinal failure transparency, attrition, and real-world generalisability. (PubMed, Clin Nutr ESPEN) - No abstract available

Journal • Real-world evidence • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 2: Evaluation of Long Term Safety and Efficacy of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=145 | Active, not recruiting | Sponsor: Zealand Pharma | Trial completion date: Oct 2026 ➔ Apr 2026 | Trial primary completion date: Oct 2026 ➔ Apr 2026

Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 3: Evaluation of Long Term Safety and Efficacy of Glepaglutide in Treatment of SBS - Extension Trial (clinicaltrials.gov) - P3 | N=129 | Active, not recruiting | Sponsor: Zealand Pharma | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Enrollment closed • Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 5: Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=90 | Not yet recruiting | Sponsor: Zealand Pharma | Initiation date: Oct 2025 ➔ Feb 2026

Trial initiation date • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 6: Efficacy and Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=35 | Enrolling by invitation | Sponsor: Zealand Pharma | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Gastrointestinal Disorder • Short Bowel Syndrome

Glucagon-Like Peptide-2 (GLP-2) Analogues in Patients With Short Bowel Syndrome Dependent on Parenteral Support: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, JGH Open) - "However, the current evidence is limited by a small number of early clinical trials, heterogeneity in dosing regimens, and a paucity of data on newer agents like glepaglutide. Further large-scale phase 3 RCTs are needed to validate the safety and efficacy of GLP-2 analogues before they can be adopted for routine clinical practice."

Journal • Retrospective data • Review • Gastrointestinal Disorder • Short Bowel Syndrome

Positive clinical outcomes associated with use of glucagon-like peptide-2 (GLP-2) analogues in patients with Intestinal Failure: a systematic review and meta-analysis. (PubMed, Clin Nutr ESPEN) - "Teduglutide appears to be an acceptable therapy, with a discontinuation rate of 14%. Early reports suggest similar benefits for emerging GLP-2 including glepaglutide and apraglutide."

Clinical data • Journal • Retrospective data • Gastrointestinal Disorder • Short Bowel Syndrome

EASE SBS 6: Efficacy and Safety Evaluation of Glepaglutide in Treatment of SBS (clinicaltrials.gov) - P3 | N=35 | Not yet recruiting | Sponsor: Zealand Pharma

New P3 trial • Gastrointestinal Disorder • Short Bowel Syndrome

Glucagon-Like Peptide Peptide-2 (GLP-2) Agonists for Patients With Short Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Our meta-analysis of six RCTs comprising 470 patients demonstrated that GLP-2 agonists significantly reduced PS volume from baseline compared to placebo (MD -251; 95% CI: -363- -139; I2 = 0%). Subgroup analyses confirmed consistent reductions in PS volume with Teduglutide and Glepaglutide, but not with Apraglutide (MD -93; 95% CI: -344 - 156). Furthermore, GLP-2 agonists nearly doubled the number of responders (defined as a ≥20% reduction in PS volume) compared to placebo (RR 1.97; 95% CI: 1.47, 2.64; I2 = 0%)."

Retrospective data • Review • Gastrointestinal Disorder • Short Bowel Syndrome