Verbiest A, Hvistendahl MK, Bolognani F, Li C, Youssef NN, Huh S, Menys A, Bhatnagar G, Vanslembrouck R, Peeters R, Sartoris R, Vermeersch P, Wauters L, Verbeke K, Jeppesen PB, Joly F, and Vanuytsel T
Background: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide., Methods: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks)., Results: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate., Conclusion: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC., Clinicaltrials: gov, Number NCT04964986., Competing Interests: Declaration of competing interest Astrid Verbiest: nothing to declare. Mark Krogh Hvistendahl: full time employee at Zealand Pharma A/S as per 01/Jun2024. Federico Bolognani: FB was an employee of VectivBio, now part of Ironwood Pharmaceuticals, Inc., at the time of the conduct of the study. Carrie Li: CL was an employee of VectivBio, now part of Ironwood Pharmaceuticals, Inc., at the time of the conduct of the study and data analysis. Nader N. Youssef: NNY was an employee of VectivBio, now part of Ironwood Pharmaceuticals, Inc., at the time of the conduct of the study. Susanna Huh: Employee of Ironwood Pharmaceuticals. Alex Menys: CEO of Motilent. Gauraang Bhatnagar: Clinical Imaging Lead at Motilent. Ragna Vanslembrouck: nothing to declare. Ronald Peeters: nothing to declare. Ricardo Sartoris: nothing to declare. Pieter Vermeersch: nothing to declare. Lucas Wauters: nothing to declare. Kristin Verbeke: nothing to declare. Palle Bekker Jeppesen: Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast A/S, Ferring Pharmaceuticals, Fresenius Kabi, GlyPharma Therapeutic, Hanmi Pharmaceuticals, Ironwood, Naia Pharmaceuticals, NPS Pharmaceuticals, Protara Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectiveBio AG, Zealand Pharma A/S Francisca Joly: has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma. Tim Vanuytsel: has served as a speaker for Baxter, Fresenius Kabi, Ironwood, VectivBio, Zealand Pharma and consultant for Agomab, Baxter, Hanmi Pharmaceuticals, Ironwood, NorthSea Therapeutics, VectivBio, Zealand Pharma., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)