O024 - LONG-TERM TREATMENT WITH ONCE-WEEKLY APRAGLUTIDE REDUCES PARENTERAL SUPPORT DEPENDENCY AND ENABLES ENTERAL AUTONOMY IN SOME PATIENTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE

O024

LONG-TERM TREATMENT WITH ONCE-WEEKLY APRAGLUTIDE REDUCES PARENTERAL SUPPORT DEPENDENCY AND ENABLES ENTERAL AUTONOMY IN SOME PATIENTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE

P. B. Jeppesen^1,*, K. Tappenden², D. Kirby³, S. Lal⁴, T. Vanuytsel⁵, C. Ming⁶, T. Masior⁶, M. Boules⁷, F. Joly⁸, K. Iyer⁹

¹Rigshospitalet, Copenhagen, Denmark, ²University of Utah Health, Salt Lake City, ³Cleveland Clinic, Cleveland, United States, ⁴The University of Manchester, Manchester, United Kingdom, ⁵UZ Leuven, Vlaams-Brabant, Belgium, ⁶Ironwood Pharmaceuticals Inc, Basel, Switzerland, ⁷Ironwood Pharmaceuticals Inc, Boston, United States, ⁸Hôpital Beaujon, Clichy, France, ⁹Mount Sinai Health System, New York, United States

Rationale: Reducing parenteral support (PS) dependency is a key treatment goal in patients with short bowel syndrome and intestinal failure (SBS-IF). We report long-term data from 3 clinical trials on the ability of the long-acting glucagon-like peptide-2 analog apraglutide (APRA) to reduce PS dependency in SBS-IF. First presented at ACG 2025, October 24–29, 2025.

Methods: Eligible patients who completed the Phase 2 STARS Nutrition (NCT04964986) or Phase 3 STARS (NCT04627025) studies could opt to continue receiving APRA (APRA/APRA) at 3.5 mg (if ≥50 kg) or 1.4 mg (if <50 kg), or switch from placebo to APRA (PBO/APRA) for up to 208 weeks in STARS Extend (NCT05018286). Endpoints included changes in PS frequency from baseline (start of APRA treatment) and proportion reaching enteral autonomy (EA; PS independence) at Weeks 52, 104, 152 and 208; and long-term safety and tolerability.

Results: As of January 2025, 166 patients (All-APRA) were analyzed (APRA/APRA: n=119; PBO/APRA: n=47). Baseline demographics and disease characteristics were generally balanced across groups. At Week 52, ≥1 day/week off PS was achieved by 49.1% (APRA/APRA) and 55.3% (PBO/APRA) of patients, with similar results for ≥2, ≥3 and ≥4 days/week off PS (Table). At Week 104 in the All-APRA group, the proportions of patients achieving ≥1, ≥2, ≥3 and ≥4 days/week off PS were 46/84 (54.8%), 42/84 (50.0%), 34/84 (40.5%) and 21/72 (29.2%), respectively. Thirty-five patients reached EA at least once; among these, most (97.1%) maintained EA for ≥3 months. APRA was well tolerated with long-term use.

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Conclusion: Long-term treatment with once-weekly APRA resulted in reductions in PS dependency that were maintained for up to 104 weeks. Most patients achieving EA sustained this for ≥3 months, without any safety concerns.

Disclosure of Interest: P. B. Jeppesen Grant / Research Support from: Palle Jeppesen has received honoraria, educational and/or grants from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast A/S, Ferring Pharmaceuticals, Fresenius Kabi, GlyPharma Therapeutic, Hanmi Pharmaceuticals, Ironwood Pharmaceuticals Inc, Naia Pharmaceuticals, NPS Pharmaceuticals, Protara Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio AG (now part of Ironwood Pharmaceuticals Inc) and Zealand Pharma, K. Tappenden Other: Kelly Tappenden serves as a board member, advisory panel or speaker for Abbott Nutrition Health Institute, Nutricia North America, Takeda Pharmaceuticals and VectivBio (now part of Ironwood Pharmaceuticals, Inc), D. Kirby Consultant for: Donald Kirby serves as a consultant or advisor for OWYN, Takeda Pharma and VectivBio (now part of Ironwood Pharmaceuticals Inc), S. Lal Grant / Research Support from: Simon Lal has received honoraria and/or educational support from Baxter, B Braun, Fresenius Kabi, NorthSea Thereapeutics, Takeda, VectivBio (now part of Ironwood Pharmaceuticals Inc) and Zealand Pharma; and has received investigator-initiated/unrestricted research grants from Baxter, Fresenius Kabi and Takeda, T. Vanuytsel Grant / Research Support from: Tim Vanuytsel has received research grants from Danone, MyHealth, Takeda and VectivBio (now part of Ironwood Pharmaceuticals Inc), Consultant for: Tim Vanuytsel serves as a consultant for Baxter, BMS, Dr. Falk Pharma, Hanmi Pharm, NorthSea Therapeutics, Takeda, Truvion, VectivBio (now part of Ironwood Pharmaceuticals Inc) and Zealand Pharma, Other: Tim Vanuytsel serves as a lecturer for Abbott, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, MyHealth, Remedus, Takeda, Truvion and VectivBio (now part of Ironwood Pharmaceuticals Inc), C. Ming Other: Chang Ming serves as an employee of Ironwood Pharmaceuticals Inc and may hold Ironwood Pharmaceuticals Inc stock, T. Masior Other: Tomasz Masior serves as an employee of Ironwood Pharmaceuticals Inc and may hold Ironwood Pharmaceuticals Inc stock, M. Boules Other: Mena Boules serves as an employee of Ironwood Pharmaceuticals Inc and may hold Ironwood Pharmaceuticals Inc stock, F. Joly Grant / Research Support from: Francisca Joly has received research funding from Baxter, Carembouche, Mobile3esolutions, Takeda Pharma, VectivBio and Zealand Pharma, Consultant for: Francisca Joly serves as a consultant or advisor for Carembouche, Hanmi, Ironwood, Mobile3esolutions, NorthSea Therapeutics, Takeda, VectivBio (now part of Ironwood Pharmaceuticals Inc) and Zealand Pharma, Other: Francisca Joly serves as a lecturer for Baxter, B Braun, Fresenius Kabi, Janssen and Theradial, K. Iyer Grant / Research Support from: Kishore Iyer has received grants from Takeda; serves as an advisor or has received grant support from VectivBio (now part of Ironwood Pharmaceuticals Inc) and NorthSea Therapeutics, Consultant for: Kishore Iyer serves as a consultant or advisor for Takeda, Speakers Bureau of: Kishore Iyer serves as a speaker or member of speakers bureau for Takeda, Other: Kishore Iyer serves as an advisor for Hanmi Pharmaceuticals