Positive topline results from global phase III trial of once-weekly apraglutide in adults with short bowel syndrome with intestinal failure (SBS-IF)

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 (NDA) 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 (-25.5% vs. -12.5%; p=0.001).

“Reducing dependency on parenteral support and easing treatment burden are important goals for every patient with SBS-IF,” said Kishore R Iyer, MBBS, FRCS (Eng), 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 (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 population (-25.6% vs. -7.8%; p<0.001). 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 (51.8% versus 44.4%) and reaching enteral autonomy in seven out of 56 (12.5%) patients versus two out of 27 (7.4%) patients on placebo.

Apraglutide was generally well-tolerated. Topline safety results were generally consistent with the safety profile demonstrated in apraglutide studies to date.

“Patients with SBS-IF bear the dual burden of a devastating condition and a complex treatment regimen that includes hours of parenteral support, which significantly impacts their quality of life and carries a risk of severe complications such as infection,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. “We believe these results demonstrate the potential for apraglutide to improve the standard of care for all adult patients with SBS dependent on parenteral support as the only GLP-2 with once-weekly administration, if approved. We are thankful to the patients and clinical investigators involved in the largest study of a GLP-2 analog in SBS-IF and will work with regulators on next steps with the goal of making apraglutide available to those living with this severe condition.”

About STARS: The STARS (STudy of ApRaglutide in SBS) pivotal Phase III trial represents the largest Phase III trial in SBS-IF to date. This 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. STARS enrolled 164 patients and dosed 163 stratified approximately 50/50 (stoma vs. colon-in continuity), then evaluated them over 24 weeks (stoma and colon-in-continuity populations) and 48 weeks (colon-in-continuity population only). Patients were randomized 2:1 to either once weekly apraglutide or placebo. The primary endpoint was relative change from baseline in actual weekly PS volume at week 24. Key secondary endpoints included patients who achieved a reduction from baseline of at least 1 day/week of PS at week 24 (all patients); relative change from baseline in actual weekly PS volume at week 24 (stoma population); patients who achieved a reduction from baseline of at least 1 day/week of PS at week 48 (colon-in-continuity population); and patients reaching enteral autonomy at week 48 (colon-in-continuity population).