Summary

Apraglutide (formerly FE 203799) is a long-acting glucagon-like peptide-2 (GLP-2) analogue engineered for once-weekly subcutaneous dosing. It is being developed for the treatment of short bowel syndrome with intestinal failure (SBS-IF), a rare condition in which patients depend on parenteral nutrition due to insufficient intestinal absorption. Phase 3 results from the STARS trial demonstrated significant reductions in parenteral nutrition volume requirements. Research use only — not licensed as a medicine in the UK.

Mechanism

Apraglutide is a long-acting GLP-2 receptor agonist. GLP-2 binds to GLP-2 receptors on intestinal enteroendocrine cells, fibroblasts, and subepithelial myofibroblasts, activating downstream signalling that promotes intestinal mucosal growth, crypt cell proliferation, villus height increase, and enhanced nutrient and fluid absorption. Key structural modifications (amino acid substitutions at positions 2, 10, 24, and 25 relative to native GLP-2) confer DPP-IV resistance and extend the half-life to ~120 hours, enabling once-weekly dosing.

Evidence base

Phase 3 (STARS, NCT04605532): Randomised, double-blind, placebo-controlled trial in adult SBS-IF patients. Statistically significant reduction in weekly PN volume versus placebo. Substantial proportion of patients achieved ≥1 day/week off PN. Full publication pending.

Phase 2: 17-patient RCT showing ~750 g/day increase in intestinal wet weight absorption and reduced PN requirements with 5 mg weekly dosing (Jeppesen et al., Lancet Gastroenterol Hepatol, 2023).

Evidence grade: Strong — Phase 3 RCT data with clinically meaningful endpoints.

Protocols

Investigational protocol (STARS Phase 3):

  • Dose: 5 mg subcutaneous, once weekly
  • Duration: 24-week treatment period
  • Route: Subcutaneous injection (abdomen or thigh)
  • Monitoring: PN volume, fluid balance, renal function, electrolytes, nutritional markers

⚠️ Research use only. Not a recommendation for self-administration.

UK Status: POM (prescription-only medicine when licensed; currently unlicensed)

Apraglutide is not licensed by the MHRA or EMA. It is an investigational product in late-stage development by Roche. Research-grade material is legal for laboratory research purposes. Not a controlled substance. Monitor MHRA/EMA for future licensing decisions.

Vendor notes

Apraglutide is a proprietary, late-stage investigational compound and is not routinely available from UK research peptide vendors. Researchers should consult licensed chemical suppliers and verify purity via certificates of analysis.

References

  1. NCT04605532 — A Study of Apraglutide in Adults With Short Bowel Syndrome With Intestinal Failure (STARS). ClinicalTrials.gov.
  2. Jeppesen PB, et al. Apraglutide, a novel long-acting GLP-2 analogue, in patients with short bowel syndrome: a Phase 2, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2023;8(3):233-243. doi:10.1016/S2468-1253(22)00390-3
  3. VectivBio AG. VectivBio announces positive topline results from STARS Phase 3 trial of apraglutide in patients with short bowel syndrome with intestinal failure. Press release, 2024.
  4. Roche Holding AG. Roche completes acquisition of VectivBio. Press release, August 2023.
  5. Berni Canani R, et al. Glucagon-like peptide-2: a review of its physiology and potential therapeutic applications. J Pediatr Gastroenterol Nutr. 2020;71(2):263-272.