Ironwood Announces Rolling Apraglutide NDA Submission for Short Bowel Syndrome

Ironwood Pharmaceuticals has announced the initiation of a New Drug Application (NDA) submission for apraglutide for the treatment of short bowel syndrome (SBS) who are dependent on parenteral support.1

Mike Shetzline, MD, PhD

Credit: Ironwood Pharmaceuticals

According to a January 29, 2025, release, in addition to initiating a rolling NDA submission, the company plans to announce new data from its open-label extension study, STARS Extend, demonstrating an increased number of patients on apraglutide achieving enteral autonomy over time. Of note, this long-term extension data will be included in the NDA, along with efficacy and tolerability data from STARS.1

“With these new data, we are even more encouraged about apraglutide’s potential to help SBS patients who are dependent on parenteral support,” said Mike Shetzline, MD, PhD, chief medical officer, senior vice president, and head of research and drug development at Ironwood.1

Data from the multicenter, double-blind, randomized, placebo-controlled phase 3 STARS trial were presented during a late-breaking session 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. It was conducted in 18 countries with enrollment from 68 study sites and is the largest global SBS-IF clinical trial to date, involving a total of 164 patients who 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.2

Ironwood previously reported the STARS 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

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.1

Of note, in order to position the company for long-term growth with apraglutide, Ironwood announced plans to reduce its workforce by approximately 50%.1

“Ironwood’s long track record of success stems from our ability to be nimble as an organization by focusing on both significant medical needs and financial performance. While LINZESS continues to grow prescription demand, given the impact of ongoing pricing pressures, we are taking steps to reduce Ironwood costs that are predominantly associated with the brand. By doing so, we believe we can continue to generate profits and cash flows and support the successful development of apraglutide,” said Tom McCourt, chief executive officer of Ironwood, who added that the company’s apraglutide launch planning is “well underway” with “strong commercial capabilities to support the future success of apraglutide, if approved.”

References

1. Ironwood Pharmaceuticals. Ironwood Pharmaceuticals initiates apraglutide NDA submission, highlights compelling new data and updates corporate structure to position for the future. January 29, 2025. Accessed January 30, 2025. https://investor.ironwoodpharma.com/press-releases/press-release-details/2025/Ironwood-Pharmaceuticals-Initiates-Apraglutide-NDA-Submission-Highlights-Compelling-New-Data-and-Updates-Corporate-Structure-to-Position-for-the-Future
2. Brooks, A. STARS: apraglutide reduces parenteral support in patients with stoma, colon-in-continuity. May 21, 2024. Accessed January 30, 2025. https://www.hcplive.com/view/stars-apraglutide-reduces-parenteral-support-in-patients-with-stoma-colon-in-continuity