Apraglutide Deemed Safe and Effective for Short Bowel Syndrome With Intestinal Failure

Jun 23, 2024

Photo Credit: Libre de droit

Patients with short bowel syndrome with intestinal failure participated in a trial that proved the safety and efficacy of apraglutide.

Apraglutide, a long-acting glucagon-like peptide-2 (GLP-2) analogue, significantly reduced parenteral support (PS) volume in patients with short bowel syndrome with intestinal failure (SBS-IF). Conducted across 73 centers in 18 countries, the trial confirmed the efficacy and safety of apraglutide in this population.

The phase 3, double-blind, placebo-controlled trial (NCT04627025) included 164 adults with SBS-IF, randomly assigned 2:1 to receive either once-weekly subcutaneous apraglutide or placebo. Dr Francisca Joly, MD, PhD, from the Hopital Beaujon, in France presented the findings.

Participants were stratified by intestinal anatomy (stoma or colon-in-continuity [CIC]) and received either 2.5 mg or 5 mg of apraglutide based on their weight. The primary endpoint was the relative change in weekly PS volume at week 24. Secondary endpoints included additional days off PS at weeks 24 and 48 and the total enteral autonomy at week 48.

The primary endpoint was met, with apraglutide-treated participants showing a significantly larger reduction in weekly PS volume at week 24 compared with placebo (-25.5% vs -12.5%; P=0.001), with the apraglutide treatment effect observed from week 8. In the stoma subgroup, the reduction was more pronounced (-25.6% vs -7.8%; P<0.001). Although the CIC subgroup showed a numerical benefit, it did not reach statistical significance (-25.2% vs -17.6%; P=0.179). A significant proportion of participants receiving apraglutide achieved an additional day off PS per week at week 24 (43% vs 27.5%; P=0.040).

Total enteral autonomy was reached in 6.4% of participants receiving apraglutide compared with 0% in the placebo group (P=0.006) at week 24. By week 48, it was reached in 12.5% in the apraglutide group compared with 7.4% in the placebo group (P=0.387). Apraglutide was well tolerated, with a low discontinuation rate due to AE’s (3.6% vs 1.9%).

“Apraglutide is the first once-weekly GLP-2 analogue to show significant efficacy in reducing PS volume in a phase 3 trial for participants with SBS-IF. The trial confirmed that apraglutide significantly reduces weekly PS volume and increases days off PS with a favourable safety profile,” Dr Joly summarised.

Medical writing support was provided by Federica Angius.