Shares of Ironwood Pharmaceuticals plunged to a 52-week low on Monday after the company announced that the U.S. Food and Drug Administration (FDA) will require an additional Phase 3 trial for apraglutide, its investigational treatment for short bowel syndrome with intestinal failure (SBS-IF).
The Boston-based gastrointestinal disease specialist saw its stock fall 37% to 59 cents in mid-morning trading, extending its year-to-date losses to 86%. The announcement represents a significant setback for the company's lead pipeline candidate.
FDA Requires Additional Data for Apraglutide Approval
Ironwood revealed that pharmacokinetic analyses conducted in preparation for its New Drug Application (NDA) indicated that the exposure and dose delivered in the original STARS Phase 3 trial were lower than planned due to issues with dose preparation and administration. Despite initially believing there was a regulatory path forward based on the strength of the STARS trial results, recent discussions with the FDA made it clear that a confirmatory Phase 3 study would be necessary.
"We are disappointed in this outcome," said Tom McCourt, CEO of Ironwood Pharmaceuticals. "We believe apraglutide has the potential to provide tremendous value to patients with SBS-IF who suffer from increased mortality and reduced quality of life."
Promising Efficacy Despite Regulatory Hurdles
Apraglutide is a once-weekly, long-acting synthetic GLP-2 analog designed to treat rare gastrointestinal diseases. The company maintains that the drug generated strong safety and efficacy data in the STARS Phase 3 trial. Notably, in the long-term extension trial, 27 apraglutide-treated patients who were dependent on parenteral support achieved enteral autonomy—the ultimate treatment goal for SBS-IF patients.
Ironwood plans to continue the long-term extension trial and believes data from the STARS trial will remain an integral part of any future NDA submission package. The company had previously initiated a rolling NDA to the FDA for apraglutide, with submission completion originally expected in the third quarter of 2025.
Strategic Review Initiated
In light of this regulatory setback, Ironwood has engaged Goldman Sachs to explore strategic alternatives to maximize shareholder value while simultaneously working with the FDA on designing the confirmatory Phase 3 trial and establishing a clear regulatory path forward.
About Short Bowel Syndrome with Intestinal Failure
Short bowel syndrome with intestinal failure is a serious condition in which patients cannot absorb sufficient nutrients and fluids from their diet due to the surgical removal or functional loss of a significant portion of the small intestine. These patients require parenteral support (intravenous nutrition) to maintain health and survival.
Current treatment options for SBS-IF are limited, creating a substantial unmet need for therapies that can reduce dependence on parenteral support and potentially achieve enteral autonomy, allowing patients to maintain nutrition through oral intake alone.
Market Impact and Future Outlook
The requirement for an additional Phase 3 trial will significantly delay apraglutide's potential market entry and increase development costs for Ironwood, which explains the severe market reaction. The company had been positioning apraglutide as a potential advancement in the treatment landscape for SBS-IF patients.
Ironwood will need to work closely with the FDA to design an appropriate confirmatory trial that addresses the dosing issues identified in the original study while leveraging the positive efficacy signals observed in both the STARS trial and its long-term extension.
