Ironwood Pharmaceuticals’ $1 billion short bowel syndrome (SBS) bet has delivered a phase 3 win—and wiped 30% off the company’s share price. While the study met its primary endpoint, the results failed to convince investors it can win out over Takeda’s Gattex, its potential generic copies and Zealand Pharma’s glepaglutide.
Boston-based Ironwood acquired the drug candidate, a long-acting GLP-2 analog, last year through its $1 billion takeover of VectaBio. Ironwood pitched the acquired molecule, apraglutide, as potentially best in class, pointing to its potency, selectivity and weekly dosing to make its case.
Now, the company has reported data from the phase 3 STARS trial, which compared once-weekly subcutaneous apraglutide to placebo in adults with SBS with intestinal failure. People with the rare and severe organ failure condition are dependent on parenteral support (PS).
After 24 weeks, the weekly volume of PS given to people on apraglutide had fallen 25.5%, compared to a 12.5% reduction in the placebo arm. The difference caused the study to hit its primary endpoint but the drug candidate will need to do more than beat placebo to make a mark commercially.
Takeda tracked (PDF) a 4.4-liter decline in PS, from a baseline of 12.9 liters, in its 24-week, daily dosing Gattex study. With the usual caveats about cross-trial comparisons, the side-by-side fails to make a strong case that apraglutide is more effective than the incumbent by that yardstick. Zealand saw a 5.13-liter drop in the twice-weekly arm of its 24-week glepaglutide trial without disclosing the baseline.
Ironwood met its first two secondary endpoints, linking apraglutide to an increase in the number of patients who had at least one day a week off PS relative to baseline and an improvement in weekly PS volume in the 50% of patients with a stoma that allows body waste to enter a drainage bag. But the trial missed its two secondary endpoints in colon-in-continuity (CIC) patients.
Ironwood estimates people with CIC account for around half of the 18,000 SBS patients globally, with the stoma subpopulation making up the rest. The potential for apraglutide to address both subpopulations is part of the company’s case for the candidate. Yet, the trial found apraglutide was no better than placebo at increasing the number of CIC patients who had at least one day a week off PS or who reached enteral autonomy at week 48.
Shares in Ironwood fell 30% to $10.50 in premarket trading from a Wednesday close of $15.12, but the company is pushing ahead with plans to file for approval of apraglutide in adults with SBS who are dependent on PS. If approved, apraglutide will go up against Gattex, the daily incumbent, and potentially Zealand’s rival long-acting candidate, which is under review at the FDA.