Ironwood reports ‘positive’ results from Phase III trial of apraglutide

Ironwood Pharmaceuticals announced positive topline results from its pivotal Phase III STARS trial, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in reducing parenteral support dependency in adult patients with short bowel syndrome with intestinal failure. SBS-IF, a rare and severe organ failure condition in which patients are dependent on PS, affects an estimated 18,000 adult patients in the U.S., Europe, and Japan. Based on these results, Ironwood plans to submit a new drug application and other regulatory filings for apraglutide for use in adult patients with SBS who are dependent on PS. The global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. The trial met its primary endpoint of relative change from baseline in actual weekly PS volume at week 24, comparing apraglutide versus placebo. “Reducing dependency on parenteral support and easing treatment burden are important goals for every patient with SBS-IF,” said Kishore R Iyer, MBBS, FRCS, FACS, Director of Adult and Pediatric Intestine Rehabilitation & Transplantation at The Mount Sinai Hospital in New York, Coordinating Principal Investigator of the trial, paid scientific advisor to Ironwood and chair of the scientific steering committee for the STARS Trial. “The STARS topline results are significant as this is the first successful Phase III placebo-controlled study in SBS-IF patients with a GLP-2 analog with once-weekly dosing.” In addition, there were four key secondary endpoints evaluated in statistical hierarchy. Apraglutide demonstrated statistical significance for the first 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 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 population. The third and fourth key secondary endpoints were specific to colon-in-continuity patients in assessing at least one day/week off PS versus baseline and reaching enteral autonomy at week 48, both of which were not achieved. Apraglutide was numerically favorable but not statistically significant relative to placebo for improving days off PS and reaching enteral autonomy in seven out of 56 patients versus two out of 27 patients on placebo. Apraglutide was generally well-tolerated. Topline safety results were generally consistent with the safety profile demonstrated in apraglutide studies to date.