P1932 - 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

Palle Jeppesen, MD, PhD¹, Kelly Tappenden, PhD, RD², Donald Kirby, MD³, Simon Lal, MD, PhD⁴, Tim Vanuytsel, MD, PhD⁵, Chang Ming, PhD⁶, Tomasz Masior, MD⁶, Mena Boules, MD⁷, Francisca Joly, MD, PhD⁸, Kishore Iyer, MBBS, FRCS⁹
1Rigshospitalet, Copenhagen University Hospital, Boston, MA; 2The University of Utah, Salt Lake City, UT; 3Cleveland Clinic Digestive Disease and Surgery Institute, Cleveland, OH; 4University of Manchester, Manchester, England, United Kingdom; 5Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, Leuven, Vlaams-Brabant, Belgium; 6Ironwood Pharmaceuticals, Inc., Basel, Basel-Stadt, Switzerland; 7Ironwood Pharmaceuticals, Inc., Boston, MA; 8Centre for Intestinal Failure, Department of Gastroenterology and Nutritional Support, Hôpital Beaujon, Clichy, Ile-de-France, France; 9Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai, New York, NY

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 p</span>rimary 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 (Table 1), with small variations in urine volume, fluid intake and body weight (Table 2). 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.

Discussion: 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.


Figure: Table 1


Figure: Table 2

Disclosures:
Palle Jeppesen: Albumedix A/S – Grant/Research Support. ArTara Therapeutics – Grant/Research Support. Bainan Biotech – Grant/Research Support. Baxter – Grant/Research Support. Coloplast A/S – Grant/Research Support. Ferring Pharmaceuticals – Grant/Research Support. Fresenius Kabi – Grant/Research Support. GlyPharma Therapeutic – Grant/Research Support. Hanmi Pharmaceuticals – Grant/Research Support. Ironwood Pharmaceuticals, Inc. (Previously VectivBio) – Grant/Research Support. Naia Pharmaceuticals – Grant/Research Support. NPS Pharmaceuticals – Grant/Research Support. Protara Therapeutics – Grant/Research Support. Shire – Grant/Research Support. Takeda – Grant/Research Support. The Novo Nordisk Foundation – Grant/Research Support. Therachon – Grant/Research Support. Zealand Pharma A/S – Grant/Research Support.
Kelly Tappenden: Abbott Nutrition Health Institute – Advisory Committee/Board Member. Ironwood Pharmaceuticals, Inc (Previously VectivBio) – Advisory Committee/Board Member. Nutricia North America – Advisory Committee/Board Member. Takeda Pharmaceuticals – Advisory Committee/Board Member.
Donald Kirby: Ironwood Pharmaceuticals, Inc. (Previously VectivBio) – Consultant. OWYN – Consultant. Takeda Pharma – Consultant.
Simon Lal: B Braun – Honoraria and/or educational support. Baxter – Grant/Research Support, Honoraria and/or educational support. Fresenius Kabi – Grant/Research Support, Honoraria and/or educational support. Ironwood Pharmaceuticals, Inc. (Previously VectivBio) – Honoraria and/or educational support. Northsea – Honoraria and/or educational support. Takeda – Grant/Research Support, Honoraria and/or educational support. Zealand – Honoraria and/or educational support.
Tim Vanuytsel: Abbott – Lecturer. Baxter – Consultant, Lecturer. Biocodex – Lecturer. BMS – Consultant. Danone – Grant/Research Support. Dr. Falk Pharma – Consultant, Lecturer. Fresenius Kabi – Lecturer. Hanmi Pharm – Consultant. Ipsen – Lecturer. Ironwood Pharmaceuticals, Inc. (Previously VectivBio) – Consultant, Grant/Research Support, Lecturer. Menarini – Lecturer. MyHealth – Grant/Research Support, Lecturer. North Sea Therapeutics – Consultant. Remedus – Lecturer. Takeda – Consultant, Grant/Research Support, Lecturer. Truvion – Consultant, Lecturer. Zealand Pharma – Consultant.
Chang Ming: Ironwood Pharmaceuticals, Inc (Previously VectivBio) – Employee.
Tomasz Masior: Ironwood Pharmaceuticals, Inc (Previously VectivBio) – Employee.
Mena Boules: Ironwood Pharmaceuticals, Inc (Previously VectivBio) – Employee, Stock-publicly held company(excluding mutual/index funds).
Francisca Joly: Baxter – Grant/Research Support, Lecturer. BBraun – Lecturer. Carembouche – Consultant, Grant/Research Support. Fresenius Kabi – Lecturer. Hanmi – Consultant. Ironwood Pharmaceuticals, Inc. (Previously VectivBio) – Consultant, Grant/Research Support. Janssen – Lecturer. Mobile3esolutions – Consultant, Grant/Research Support. NorthSea Therapeutics – Consultant. Takeda – Consultant, Grant/Research Support. Theradial – Consultant. Zealand – Consultant, Grant/Research Support.
Kishore Iyer: Hanmi Pharmaceuticals – Advisor or Review Panel Member. Ironwood Pharmaceuticals, Inc. (Previously VectivBio) – Advisor or Review Panel Member, Grant/Research Support. Northsea Therapeutics – Advisor or Review Panel Member, Grant/Research Support. Takeda Pharma – Consultant, Grant/Research Support, Speakers Bureau.

Palle Jeppesen, MD, PhD¹, Kelly Tappenden, PhD, RD², Donald Kirby, MD³, Simon Lal, MD, PhD⁴, Tim Vanuytsel, MD, PhD⁵, Chang Ming, PhD⁶, Tomasz Masior, MD⁶, Mena Boules, MD⁷, Francisca Joly, MD, PhD⁸, Kishore Iyer, MBBS, FRCS⁹. P1932 - 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, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.