S3057 Long-Term Treatment With Once-Weekly Apraglutide Reduces Parenteral Support Volume and Increases Clinical Responder Rates in Patients With Short Bowel Syndrome and Intestinal Failure: The STARS Extend Trial

Introduction: Patients with short bowel syndrome and intestinal failure are dependent on parenteral support (PS) to meet nutritional and/or fluid requirements. Apraglutide (APRA), a long-acting glucagon-like peptide-2 (GLP-2) analog administered subcutaneously once-weekly, stimulates intestinal adaptation and has been shown to reduce PS requirements in the open-label, phase 2 metabolic balance study STARS Nutrition (NCT04964986) and the phase 3, randomized, double-blind STARS study (NCT04627025). STARS Extend (NCT05018286) is an open-label, long-term extension (LTE) trial designed to evaluate the long-term safety of APRA and determine whether treatment effects are maintained in the long term. Methods: Patients who completed STARS Nutrition or STARS without meeting stopping criteria could enroll in STARS Extend, either switching to APRA for those previously on placebo (PBO) or continuing to receive APRA (APRA/APRA group). APRA was given at a dose of 3.5 mg if patient ≥50 kg or 1.4 mg if <50 kg, for up to 208 weeks. The primary objective was to assess long-term safety and tolerability; secondary endpoints included changes from baseline (BL; defined as start of APRA treatment in weekly PS volume and proportion of clinical responders (≥20% reduction) and high responders (≥40% reduction) at weeks 52, 104, 152, and 208. Results: As of January 2025, 166 patients were analyzed (APRA/APRA, n = 119; PBRO/APRA, n = 47). BL demographics and disease characteristics were generally balanced across groups. Reductions in weekly PS volume from BL were similar in both groups (-36.1% vs -39.1% at week 52 for APRA/APRA vs PBO/APRA), with small variations in urine volume, fluid intake and body weight. The proportion of clinical responders was high in both groups (67.9% vs 68.4% for APRA/APRA and PBO/APRA at week 52), with rates of 44.3% vs 50.0% for clinical high responders. APRA was well tolerated with long-term use; discontinuation of APRA due to adverse events (AEs) occurred in 6.7% (8/119) of patients in the APRA/APRA group and 2.1% (1/47) of those in the PBO/APRA group. No AEs led to dose reduction, and study discontinuation due to AEs occurred in 1 patient in each group. Conclusion: Long-term treatment with once-weekly APRA resulted in sustained reductions in relative percentage change in weekly PS volume from BL of 48% at week 104, and high clinical responder rates. APRA was well tolerated throughout the treatment period.