66: Glepaglutide Induces Meaningful Clinical Improvement In Patients With Short Bowel Syndrome Chronic Intestinal Failure: Results Of A Phase 3 Trial

Introduction: Management of patients with short bowel syndrome (SBS) and intestinal failure (IF) targets clinical and patient-centric outcomes including reducing need for parenteral support (PS) and improved quality of life (QoL). Glepaglutide is a novel long-acting GLP-2 analog. We conducted a phase 3 trial to evaluate the efficacy and safety (EASE) of glepaglutide in reducing the need for PS and improving QoL in patients with SBS chronic IF (SBS-CIF). Methods: EASE SBS 1 is a multi-center, placebo-controlled, randomized, parallel-group, double-blind phase 3 trial (NCT:03690206). Key inclusion criteria were SBS-CIF adult patients with requirement for PS at least 3 days/week. Patients were randomized 1:1:1 to 24 weeks of treatment with subcutaneous injections of either 10 mg glepaglutide twice-weekly (TW), 10 mg once-weekly (OW), or placebo. PS volume requirements were evaluated and adjusted using regular fluid balance periods. Primary endpoint was change in weekly PS volume from baseline to 24 weeks. Key secondary efficacy endpoints included percentage of patients achieving clinical response (at least 20% reduction in PS), reduction in days on PS ≥1 day/week, and number of patients achieving oral/enteral autonomy (total PS weaning) at week 24. Patient Global Impression of Change (PGIC), a patient-reported outcome (PRO) tool, where patients rate their change in overall status since start of the trial on a 7-point Likert scale, was assessed at week 24. Results: 106 patients were randomized and 102 completed the trial. Treatment arms were well-balanced for patient demographics and baseline characteristics. Glepaglutide TW treatment significantly reduced PS requirements vs. placebo (mean change of -5.13 vs. -2.85 L/week; estimated difference of -2.28 L/week [-3.83; -0.73]95% CI; p=0.0039). Glepaglutide TW was also superior vs. placebo for proportion of patients achieving clinical response (65.7% vs. 38.9%; estimated difference of 26.6% [4.3; 48.9]95% CI; p=0.0243), and percentage of patients achieving a reduction in days on PS ≥1 day/week (51.4% vs. 19.4%; estimated difference of 31.7% [11.4; 51.9]95% CI; p=0.0043). No statistically significant difference was established for glepaglutide OW vs. placebo, however a dose-dependent trend was observed. Of special note, total PS weaning was achieved for 5 (14%), 4 (12%) and 0 patients receiving glepaglutide TW, OW and placebo, respectively. Improvement in PRO using PGIC was shown with significant differences relative to placebo for both glepaglutide TW (p=0.0020) and OW (p<0.0001). Glepaglutide was assessed to be safe and well-tolerated. More adverse events were reported in the glepaglutide treatment groups than for placebo, primarily attributable to mild injection site reactions. Conclusions: Glepaglutide treatment of SBS-CIF patients was assessed to be safe and well-tolerated resulting in meaningful improvement in clinical and patient-centric outcomes (PS needs, oral/enteral autonomy, and PRO).