Ironwood Pharmaceuticals, Inc. will present late-breaking data during the 2024 Digestive Disease Week® (DDW) meeting from its pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in adult patients with short bowel syndrome with intestinal failure (SBS-IF). These findings build on the positive topline data that Ironwood previously announced in February 2024. Based on these results, the company is working to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and marketing applications to other regulatory agencies for apraglutide for the treatment of adult patients with SBS who are dependent on parenteral support (PS).

SBS-IF, a rare chronic debilitating malabsorptive condition in which patients are dependent on PS, affects an estimated 18,000 adult patients in the U.S., Europe, and Japan. Apraglutide is the first and only investigational once-weekly GLP-2 analog that has successfully demonstrated positive results in a Phase III placebo-controlled study. The late-breaking data at DDW are from the largest global SBS-IF clinical trial conducted to date and are being shared during an oral presentation titled ?Efficacy and Safety of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Results from the STARS Study - A Global Phase 3 Double-Blind, Randomized, Placebo-Controlled Trial.?

Ironwood previously reported that the STARS clinical trial met its primary endpoint of relative change from baseline in actual weekly PS volume at week 24 vs. placebo (-25.5% vs. -12.5%; p=0.001), driven by both stoma and colon-in-continuity subpopulations.

Treatment effect with relative PS volume reduction was observed from week 8 onward (-8% vs -1.6% placebo, p=0.002). Findings from the late-breaking presentation include: Significantly more apraglutide-patients gained additional days off from PS per week at week 24 versus placebo (=2 days: 24.5% vs 11.3%, p=0.021; =3 days: 11.8% vs 1.9%, p=0.006). Significantly more apraglutide-treated patients in the overall and the stoma populations were clinical responders and clinical high responders (defined as =20% and =40% PS volume reduction, respectively), at both weeks 20 and 24 versus placebo; Overall population: Clinical responders 42.7% vs 20.8%, p=0.003; Clinical high responders 22.7% vs 9.4%, p=0.018; Stoma subpopulation: clinical responders 40.7% vs 15.4%, p=0.02; clinical high responders 20.4% vs 0%, p=0.009; Seven apraglutide-treated patients achieved enteral autonomy (three in the stoma subpopulation, four in the colon-in-continuity subpopulation) by week 24 (6.4% apraglutide vs 0% placebo, p=0.006).

Three additional colon-in-continuity patients achieved enteral autonomy by week 48: 7/56 [12.5%] apraglutide vs 2/27 placebo [7.4%], p=0.387. Apraglutide also demonstrated statistical significance on two key secondary endpoints, with more patients in the combined population achieving at least one day/week off PS relative to baseline at week 24 versus placebo (43.0% vs. 27.5%; p=0.040) and more patients treated with apraglutide versus placebo demonstrating improvement in relative change from baseline in actual weekly PS volume at week 24 in the stoma subpopulation (-25.6% vs.

-7.8%; p<0.001). Apraglutide was well-tolerated, with no new safety signals identified and the safety profile was consistent with previous apraglutide studies. In addition to the STARS Phase III oral presentation, Ironwood, and its collaborators presented data highlighting findings across the apraglutide development program.