S3026 Long-Term Treatment With Once-Weekly Apraglutide Reduces Parenteral Support Dependency and Allows to Reach Enteral Autonomy in Some Patients With Short Bowel Syndrome and Intestinal Failure: The STARS Extend Trial

Introduction: Reducing parenteral support (PS) dependency (fewer days on PS per week) is a key treatment goal in patients (pts) with short bowel syndrome and intestinal failure, with achieving enteral autonomy (PS independence) being the ultimate goal. The long-acting glucagon-like peptide-2 (GLP-2) analog apraglutide (APRA) administered subcutaneously once weekly showed efficacy in reducing PS needs in phase 2 STARS Nutrition and phase 3 STARS trials. STARS Extend (NCT05018286), an open-label, long-term extension (LTE) study, aims to assess the long-term safety and tolerability of APRA, and whether treatment effects are maintained in the long term. Methods: Eligible pts who completed STARS or STARS Nutrition could opt to continue APRA (APRA/APRA) at dose of 3.5 mg if pt ≥50 kg or 1.4 mg if <50 kg, or switch from placebo (PBO/APRA), for up to 208 weeks in STARS Extend. The primary objective was long-term safety and tolerability; secondary endpoints included changes in PS frequency and pts reaching enteral autonomy at weeks 52, 104, 152, and 208. Baseline (BL) was start of APRA treatment. Results: As of January 2025, 166 pts were analyzed (APRA/APRA: 119; PBRO/APRA: 47). BL demographics and disease characteristics were generally balanced across groups. At week 52, ≥1 day/week off PS was achieved by 49.1% and 55.3% of APRA/APRA and PBO/APRA pts, with small variations in urine volume, fluid intake and body weight. Similar results were observed at week 104 (55.4% vs 50.0%), and for ≥2, ≥3, and ≥4 days/week off PS. 35 pts reached enteral autonomy at least once (24 [20.2%] in APRA/APRA and 11 [23.4%] in PBO/APRA). Of those, 83.3% (20/24) and 90.9% (10/11) maintained continuous EA through last follow-up. Among those achieving enteral autonomy, 24/24 (100%) and 10/11 (90.9%), and 20/24 (83.3%) and 8/11 (72.7%) maintained it for ≥3 and ≥6 months, respectively, in APRA/APRA and PBO/APRA. Body weight at enteral autonomy did not vary from baseline (68.24 kg vs 67.09 kg overall). APRA was well tolerated, with most adverse events being Grade 1/2. Conclusion: Long-term treatment with once-weekly APRA resulted in continued reductions in PS dependency. It led to sustained enteral autonomy, a critical milestone in potentially reducing burden of care and improving QoL, highlighting the potential for ongoing clinical benefit with long-term therapy.