O023 - SUBGROUP ANALYSIS OF CHANGE IN PARENTERAL SUPPORT VOLUME NEEDS IN PATIENTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE FOLLOWING TREATMENT WITH GLEPAGLUTIDE

O023

SUBGROUP ANALYSIS OF CHANGE IN PARENTERAL SUPPORT VOLUME NEEDS IN PATIENTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE FOLLOWING TREATMENT WITH GLEPAGLUTIDE

T. Vanuytsel^1,*, P. B. Jeppesen², T. S. Nielsen³, M. Berner-Hansen^3,4, B. Santacruz³, L. B. Graff³, D. F. Mercer⁵

¹Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Leuven, Leuven, Belgium, ²Rigshospitalet University Hospital, Copenhagen, ³Zealand Pharma A/S, Soeborg, ⁴Digestive Disease Centre, Bispebjerg University Hospital, Copenhagen, Denmark, ⁵Department of Surgery, University of Nebraska Medical Center, Nebraska, United States

Rationale: Glepaglutide is a novel long-acting glucagon-like peptide (GLP)-2 analogue under development to reduce the need for or dependence on parenteral support (PS) in patients with short bowel syndrome and intestinal failure (SBS-IF). Patient characteristics could impact the magnitude of absolute changes of PS volume following glepaglutide therapy.

Methods: Patients in the EASE SBS-1 phase 3 trial were randomized to receive glepaglutide 10 mg subcutaneously once weekly (OW), twice weekly (TW) or placebo for 24 weeks. Predefined subgroup analyses for primary endpoint (change in weekly PS volumes from baseline to week 24) were only performed if there were ≥5 patients per treatment group in each subgroup. The subgroups satisfying this criterion were PS volume at baseline, age, sex, SBS anatomical classification, BMI, stoma, days on PS, renal and hepatic impairment. Subgroups were analyzed with a mixed model for repeated measures.

Results: As previously communicated, glepaglutide TW significantly reduced weekly PS volumes from baseline to week 24 vs placebo (mean change, -5.13 vs -2.85 L/wk; P=0.0039). No significant difference was found for glepaglutide OW vs placebo. Across subgroups, all estimated treatment differences relative to placebo were in favor of glepaglutide TW, and no notable subgroup effects were identified. Importantly, efficacy was independent of anatomical subgroup (stoma or colon-in-continuity), renal and hepatic function.

Conclusion: For all subgroups analyzed, the estimated treatment differences favored glepaglutide 10mg TW versus placebo, with apparent similar efficacy across subgroups. Accordingly, neither intestinal anatomy, renal function nor hepatic impairment affected changes in PS volume needs induced by glepaglutide. Results support the relevance of glepaglutide therapy in the broad and heterogenous SBS patient population.

Disclosure of Interest: T. Vanuytsel Grant / Research Support from: Abbott, Baxter Healthcare Corporation, Fresenius Kabi, Hanmi Pharmaceuticals, Ironwood, NorthSea Therapeutics, Takeda, VectivBio, and Zealand Pharma and has received research funding from Ironwood, Takeda and VectivBio, P. B. Jeppesen: None declared, T. S. Nielsen: None declared, M. Berner-Hansen: None declared, B. Santacruz: None declared, L. B. Graff: None declared, D. F. Mercer: None declared