STARS: Apraglutide Reduces Parenteral Support in Patients with Stoma, Colon-In-Continuity

Ironwood Pharmaceuticals has announced new data from the phase 3 STARS trial evaluating the safety and efficacy of once-weekly subcutaneous apraglutide in patients with short bowel syndrome with intestinal failure (SBS-IF).¹

The data was presented in a late-breaking abstract at Digestive Disease Week (DDW) 2024 in Washington, DC, and showed significantly more patients treated with apraglutide gained additional days off from parenteral support per week and were clinical responders or clinical high responders, building upon previous positive topline data announced earlier in 2024.^1,2

“Given the burden that parenteral support places on people living with SBS-IF, the goal of treatment is to importantly gain additional days off PS, and ultimately achieve enteral autonomy in those who can achieve it,” Kishore Iyer, MBBS, director of adult and pediatric intestine rehabilitation and transplantation at Mount Sinai Hospital and coordinating principal investigator of the trial, said in a press release.¹ “The fact that some CIC and stoma patients on apraglutide achieved enteral autonomy at week 24 and sustained that autonomy through 48 weeks is an important outcome and demonstrates the potential of apraglutide for these patients.”

According to a release from Ironwood, based on these results, the company plans to submit a New Drug Application (NDA) to the US Food and Drug Administration and marketing applications to other regulatory agencies for apraglutide for the treatment of adult patients with SBS who are dependent on parenteral support.¹

Apraglutide is an investigational, next-generation, long-acting synthetic GLP-2 analog in development for multiple rare gastrointestinal diseases, including SBS-IF and Acute Graft-Versus-Host Disease (aGVHD). Of note, it is the first and only investigational once-weekly GLP-2 analog that has successfully demonstrated positive results in a phase 3 placebo-controlled study.¹

A multicenter, double-blind, randomized, placebo-controlled trial, STARS was conducted in 18 countries with enrollment from 68 study sites and is the largest global SBS-IF clinical trial to date. A total of 164 patients were randomly assigned in a 2:1 ratio to receive once weekly apraglutide or placebo, stratified by remnant bowel anatomy and evaluated over 24- and 48-week periods.¹

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 at least 1 day/week off parenteral support at week 24; relative change from baseline in actual weekly parenteral support volume at week 24; patients who achieved a reduction from baseline of at least 1 day/week off parenteral support at week 48; and patients reaching enteral autonomy at week 48.¹

Ironwood previously reported the STARS clinical trial met its primary endpoint of relative change from baseline in actual weekly parenteral support volume at week 24 compared to placebo (-25.5% vs -12.5%; P = .001), driven by both stoma and colon-in-continuity subpopulations. Additionally, treatment effect with relative parenteral support volume reduction was observed from week 8 onward (-8% vs -1.6%; P = .002).^1,2

Data presented at DDW showed significantly more apraglutide patients gained additional days off from parenteral support per week at week 24 versus placebo (≥2 days, 24.5% vs 11.3%; P = .021 and ≥3 days, 11.8% vs 1.9%; P = .006). Additionally, significantly more patients treated with apraglutide were clinical responders and clinical high responders, defined as ≥20% and ≥40% parenteral support volume reduction, respectively, at both weeks 20 and 24 versus placebo. Investigators pointed out this was consistent across both the overall (Clinical responders, 42.7% vs 20.8%; P = .003; Clinical high responders, 22.7% vs 9.4%; P = .018) and the stoma populations (Clinical responders, 40.7% vs 15.4%; P = .02; Clinical high responders, 20.4% vs 0%; P = .009).¹

Enteral autonomy was achieved by 7 apraglutide-treated patients by week 24, including 3 in the stoma subpopulation and 4 in the colon-in-continuity subpopulation (6.4% apraglutide vs 0% placebo; P = .006). By week 48, an additional 3 colon-in-continuity patients achieved enteral autonomy (12.5% apraglutide vs 7.4% placebo; P = .387).¹

Investigators noted apraglutide also demonstrated statistical significance for 2 key secondary endpoints, with more patients in the combined population achieving ≥ 1 day/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 subpopulation (-25.6% vs -7.8%; P <.001).¹

Apraglutide was well-tolerated, with no new safety signals identified and a safety profile consistent with previous apraglutide studies. According to the release, Ironwood is working to submit an NDA for apraglutide for the treatment of adult patients with SBS.¹

“The apraglutide findings showcase the breadth and depth of positive clinical trial outcomes with this compound to date, with the strength of the Phase III data enabling a strong submission and a path to potential FDA and other regulatory approvals,” said Michael Shetzline, MD, PhD, chief medical officer, senior vice president, and head of research and drug development at Ironwood Pharmaceuticals.¹ “We’re excited for the opportunity to unlock a new and potentially differentiated treatment option for adult patients with SBS dependent on parenteral support.”

References:

1. ^{Ironwood Pharmaceuticals. Ironwood Late-Breaker Oral Presentation at Digestive Disease Week® Reinforces Potential of Once-Weekly Apraglutide for Adults with Short Bowel Syndrome with Intestinal Failure (SBS-IF). May 21, 2024. Accessed May 21, 2024. https://investor.ironwoodpharma.com/press-releases/press-release-details/2024/Ironwood-Late-Breaker-Oral-Presentation-at-Digestive-Disease-Week-Reinforces-Potential-of-Once-Weekly-Apraglutide-for-Adults-with-Short-Bowel-Syndrome-with-Intestinal-Failure-SBS-IF/default.aspx}
2. ^{Brooks, A. Apraglutide Meets Primary Endpoint for Parenteral Support Reduction in Phase 3 STARS Trial. HCPLive. February 29, 2024. Accessed May 21, 2024. https://www.hcplive.com/view/apraglutide-meets-primary-endpoint-parenteral-support-reduction-phase-3-stars-trial}