Apraglutide Meets Primary Endpoint for Parenteral Support Reduction in Phase 3 STARS Trial

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Positive topline results show apraglutide outperformed placebo for relative change from baseline in actual weekly parenteral support volume at week 24 in adults with SBS-IF.

Kishore R Iyer, MBBS, FRCS, FACS | Credit: Mount Sinai

Kishore R Iyer, MBBS, FRCS, FACS

Credit: Mount Sinai

Ironwood Pharmaceuticals has announced positive topline results from the phase 3 STARS trial of once-weekly subcutaneous apraglutide for reducing parenteral support dependency in adult patients with short bowel syndrome with intestinal failure (SBS-IF).1

According to the February 29 release, the trial met its primary endpoint for relative change from baseline in actual weekly parenteral support volume at week 24, with apraglutide (-25.5%) outperforming placebo (-12.5%; P = .001). Based on these results, Ironwood plans to submit a New Drug Application and other regulatory filings for the use of apraglutide in adult patients with SBS who are dependent on parenteral support.1

“Reducing dependency on parenteral support and easing treatment burden are important goals for every patient with SBS-IF,” Kishore R Iyer, MBBS, FRCS, FACS, director of Adult and Pediatric Intestine Rehabilitation and Transplantation at Mount Sinai Hospital and coordinating principal investigator of the trial, said in the press release.1 “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.”

An investigational, long-acting synthetic glucagon-like peptide-2 (GLP-2) analog, apraglutide is in development for a range of rare gastrointestinal diseases where GLP-2 can play a central role in addressing disease pathophysiology, including SBS and acute graft versus host disease. Positive final data from the phase 2 STARS Nutrition program were presented during a late-breaker oral presentation at United European Gastroenterology (UEG) Week 2023, highlighting its acceptable safety profile and ability to improve intestinal absorption as indicated by 50% parenteral support volume and energy content decrease, resulting in 1 or more days off parenteral support.1,2

A global, multicenter, double-blind, randomized, placebo-controlled trial, STARS evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. With 164 patients enrolled and 163 dosed, STARS represents the largest phase 3 trial in SBS-IF to date.1

According to the release, participants were stratified approximately 50/50 (stoma vs colon-in continuity) and evaluated over 24 weeks. The colon-in-continuity population was evaluated over 48 weeks. Patients were randomized in a 2:1 ratio to either once weekly apraglutide or placebo. The primary endpoint was relative change from baseline in actual weekly parenteral support volume at week 24. Key secondary endpoints included:

  • Patients who achieved a reduction from baseline of ≥ 1 day per week of parenteral support at week 24 (all patients)
  • Relative change from baseline in actual weekly parenteral support volume at week 24 (stoma population)
  • Patients who achieved a reduction from baseline of at least 1 day/week of parenteral support at week 48 (colon-in-continuity population)
  • Patients reaching enteral autonomy at week 48 (colon-in-continuity population).

Apraglutide demonstrated statistical significance for the first 2 key secondary endpoints, with more patients in the combined population achieving ≥ 1 day per week off parenteral support relative to baseline at week 24 versus placebo (43.0% vs 27.5%; P = .040) and more patients treated with apraglutide versus placebo demonstrating improvement in relative change from baseline in actual weekly parenteral support volume at week 24 in the stoma population (-25.6% vs -7.8%; P <.001).1

Although apraglutide was numerically favorable for the third and fourth key secondary endpoints specific to colon-in-continuity patients in assessing ≥ 1 day per week off parenteral support versus baseline (51.8% vs 44.4%) and reaching enteral autonomy at week 48 (12.5% vs 7.4%), these results were not statistically significant relative to placebo.1

According to the release, apraglutide was generally well-tolerated with safety results generally consistent with the safety profile demonstrated in apraglutide studies to date.1

“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, MD, PhD, chief medical officer, senior vice president, and head of research and drug development at Ironwood Pharmaceuticals.1 “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.”

References:

  1. Ironwood Pharmaceuticals. Ironwood Pharmaceuticals Announces Positive Topline Results from Global Phase III Trial of Once-Weekly Apraglutide in Adults with Short Bowel Syndrome with Intestinal Failure (SBS-IF). Press Releases. February 29, 2024. Accessed February 29, 2024. https://investor.ironwoodpharma.com/press-releases/press-release-details/2024/Ironwood-Pharmaceuticals-Announces-Positive-Topline-Results-from-Global-Phase-III-Trial-of-Once-Weekly-Apraglutide-in-Adults-with-Short-Bowel-Syndrome-with-Intestinal-Failure-SBS-IF/default.aspx
  2. Brooks, A. Apraglutide Reduces Parenteral Support Dependency in Patients with SBS-IF, CIC. HCPLive. October 19, 2023. Accessed February 29, 2024. https://www.hcplive.com/view/apraglutide-reduces-parenteral-support-dependency-in-patients-with-sbs-if-cic
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