Ironwood Pharmaceuticals is mulling its options after the FDA demanded another phase 3 trial before it will make an approval decision on the biopharma’s long-acting GLP-2 analog.
The drug developer initiated a rolling approval application in January for the candidate, called apraglutide, for the treatment of short bowel syndrome (SBS) patients who are dependent on parenteral support (PS), a necessary intravenous treatment for people with severe organ failure conditions. In order to “streamline” its focus on apraglutide, the company also announced at the same time that it was halving its workforce.
That application was based on a caveated phase 3 win for the drug last year, as well as long-term extension data from 27 apraglutide-dosed patients who were able to stop relying on intravenous nutrition.
But in this morning’s release, Ironwood explained that the company’s own pharmacokinetic analysis of the original trial data had revealed that the exposure and dose of apraglutide delivered in the study “were lower than planned due to dose preparation and administration.”
Despite this, Ironwood had been confident there was a regulatory path forward for the drug. Now, however, recent discussions with the FDA made it "clear that a confirmatory phase 3 trial is needed to seek approval," according to the company.
The biopharma said it plans to work with the FDA on the design of this new trial. But alongside this work, Ironwood has now engaged Goldman Sachs “to explore strategic alternatives for the company to maximize value for stockholders.”
The company may take some comfort from the fact that Zealand Pharma’s bid for approval of its own GLP-2 analog SBS treatment was also batted away in December by the FDA, who demanded another trial after citing a lack of evidence.
“We are disappointed in this outcome, as we firmly believe apraglutide has the potential to provide tremendous value to patients with SBS-IF who suffer from increased mortality, and reduced quality of life, and will now have to wait for the results of a confirmatory phase 3 trial,” Ironwood’s CEO Tom McCourt said in this morning's release.
“We are focused on the best path forward to get apraglutide to market, which we believe still has the potential to be a blockbuster drug,” McCourt added. “Concurrently, we will be exploring strategic alternatives for the company in an effort to maximize stockholder value.”
The biotech acquired apraglutide in 2023 through the $1 billion takeover of VectaBio. Ironwood believes the candidate could serve as a best-in-class drug, touting the investigational treatment’s potency, selectivity and weekly dosing.
Apraglutide’s phase 3 win last year saw the once-weekly subcutaneous treatment tied to a 25.5% decrease in weekly PS volume at 24 weeks, compared to a 12.5% reduction in the placebo arm, hitting the study’s main goal. The trial also met its first two secondary endpoints, tying 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 study missed two secondary endpoints in colon-in-continuity (CIC) patients. People with CIC make up about half of the 18,000 SBS patients worldwide, with the stoma subpopulation accounting for the other half. At the time, investors remained skeptical that the treatment could best Takeda’s Gattex.
Ironwood returned with subgroup data later in the year that aimed to counter the CIC patient disparity, showing a consistent treatment effect for apraglutide across patients with stoma and CIC.