Ironwood Presents Apraglutide Data for SBS-IF at Digestive Disease Week®

Ironwood Pharmaceuticals, Inc., a healthcare company focusing on gastrointestinal (GI) conditions, will present breakthrough data from its pivotal Phase III STARS clinical trial during the 2024 Digestive Disease Week (DDW) meeting. This study evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in adults with short bowel syndrome with intestinal failure (SBS-IF). The latest findings reinforce the previously announced positive results from February 2024, encouraging Ironwood to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and other regulatory bodies for apraglutide's use in SBS patients reliant on parenteral support (PS).

SBS-IF is a rare, chronic condition marked by severe malabsorption, necessitating PS. It affects about 18,000 adults across the U.S., Europe, and Japan. Apraglutide emerges as the first investigational GLP-2 analog administered weekly, achieving success in Phase III trials.

The STARS trial is the largest global SBS-IF study to date. The key findings were presented in an oral session titled "Efficacy and Safety of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Results from the STARS Study - A Global Phase 3 Double-Blind, Randomized, Placebo-Controlled Trial." The trial achieved its primary endpoint, showing a significant reduction in weekly PS volume by week 24 compared to placebo, with notable results in both stoma and colon-in-continuity (CIC) subpopulations.

Highlights from the presentation include:
- By week 24, a higher percentage of apraglutide-treated patients had additional days off from PS compared to placebo (≥2 days: 24.5% vs. 11.3%, p=0.021; ≥3 days: 11.8% vs. 1.9%, p=0.006).
- Significantly more apraglutide-treated patients were clinical responders (≥20% PS volume reduction) and high responders (≥40% PS volume reduction) at weeks 20 and 24.
- Seven patients achieved enteral autonomy by week 24, with continued improvement in the CIC subpopulation by week 48.

Dr. Kishore R Iyer, who played a pivotal role in the trial, emphasized the goal of SBS-IF treatment is to lessen PS dependence, ultimately aiming for enteral autonomy. The trial's results indicate that apraglutide can potentially provide significant benefits to SBS-IF patients, offering a path to fewer PS requirements and improved quality of life.

The study also demonstrated statistical significance in key secondary endpoints. More patients achieved at least one day off PS per week at 24 weeks, and the stoma subpopulation showed notable improvement in PS volume reduction. Apraglutide was well-tolerated, with no new safety concerns, aligning with previous studies.

Dr. Michael Shetzline, Ironwood's Chief Medical Officer, highlighted the positive outcomes of the apraglutide trials and the potential for regulatory approvals. The data supports Ironwood's commitment to advancing treatments for GI diseases.

Additionally, Ironwood and its partners presented findings from the STARS Nutrition study, which evaluated apraglutide's impact on intestinal absorption in SBS-IF patients with CIC. The study showed apraglutide's role in increasing bowel length and improving patient-reported outcomes, including PS weaning and better nutrient absorption.

Other presentations at the DDW meeting included studies on the impact of apraglutide on gastric emptying, irritable bowel syndrome with constipation (IBS-C), and functional constipation, emphasizing the broad potential of apraglutide in treating various GI conditions.

In summary, Ironwood Pharmaceuticals' Phase III STARS trial has shown promising results for apraglutide in treating SBS-IF, leading to significant reductions in PS, improved patient outcomes, and paving the way for potential regulatory approvals.