Kishore Iyer, MBBS, MSc: Defining Short Bowel Syndrome, What Apraglutide Could Offer

Patients with short bowel syndrome and intestinal failure (SBS-IF) depend on parenteral support to meet nutritional and fluid requirements, but new research suggests apraglutide may be a viable treatment option for stimulating intestinal adaptation and reducing dependence on parenteral support regardless of baseline demographics and disease-specific characteristics.

The research was presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania, by Kishore Iyer, MBBS, MSc, FRCS(Eng), FACS, director of adult and pediatric intestinal rehabilitation and transplantation at Mount Sinai, and builds upon previous data from the phase 3 STARS trial of once-weekly subcutaneous apraglutide in patients with SBS-IF.

In an interview with HCPLive, Iyer was careful to describe the difference between SBS and IF, saying “While we sometimes use the term short bowel syndrome and intestinal failure interchangeably, they're not the same. The large subset of patients with short bowel syndrome who need intravenous fluid support are the ones who have intestinal failure.”

A short-acting recombinant glucagon like peptide-2 (GLP-2), teduglutide has been shown to help patients with SBS-IF decrease their intravenous fluid support requirements and decrease their parenteral support but has a relatively short half life and is given by daily subcutaneous injection.

Findings from the global, phase 3, double-blind, placebo-controlled STARS trial confirmed the safety and efficacy of apraglutide, an investigational, next-generation, long-acting synthetic GLP-2 analog, for the treatment of SBS-IF. Specifically, results showed significantly more patients treated with apraglutide gained additional days off from parenteral support per week and were clinical responders or clinical high responders. Now, additional findings from a subgroup of the STARS trial confirm apraglutide’s benefit regardless of demographics and disease characteristics.

“What is really exciting about apraglutide is that it appears to have greater specificity for the GLP-2 receptor cells and and it has some interesting pharmacokinetic and pharmacodynamic properties with a long half life that allows it to be given once a week with all the potentially beneficial effects of GLP-2,” Iyer explained.

Editors’ note: Iyer has relevant disclosures with Hanmi Pharmaceuticals, Northsea Therapeutics, Takeda Pharmaceuticals, and VectivBio (now part of Ironwood Pharmaceuticals).

References

1. ^{Iyer K, Joly F, Kirby D, et al. 19 - Phase 3, Double-Blind, Randomized STARS Trial of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Subgroup Analyses by Baseline Demographics and SBS Disease Characteristics. Presented at: American College of Gastroenterology (ACG) 2024 Scientific Sessions. Philadelphia, PA. October 25 – 30, 2024.}
2. ^{Brooks, A. STARS: Apraglutide Reduces Parenteral Support in Patients with Stoma, Colon-In-Continuity. HCPLive. May 21, 2024. Accessed October 29, 2024. https://www.hcplive.com/view/stars-apraglutide-reduces-parenteral-support-in-patients-with-stoma-colon-in-continuity}