Ironwood crashes down as FDA seeks new phase 3 trial
Shares in Ironwood Pharma fell by a third after it revealed that the FDA is insisting on a new phase 3 trial of its short bowel syndrome therapy before it can consider approval.
The outcome of its discussions with the US regulator is far from what the company was hoping for, and it has now started a review of its "strategic options" – with the help of Goldman Sachs – to try to chart its path forward. That follows a halving of its headcount in January.
A year ago, Ironwood reported the results of its phase 3 STARS trial of GLP-2 analogue apraglutide as a treatment for short bowel syndrome with intestinal failure (SBS-IF), a rare and severe condition in which patients become dependent on parenteral support (PS), in some cases needing infusions of parenteral nutrition for up to 15 hours per day. It affects an estimated 18,000 adult patients in the US, Europe, and Japan.
Apraglutide hit its primary endpoint in the study, reducing the volume of PS needed by patients by 25.5% at 24 weeks, compared to a 12.5% decline for the placebo group, and also improved two of four secondary endpoints, increasing the chances that patients with SBS-IF could have at least one day free of PS in a week and reducing the need for PS in patients with a stoma fitted.
The FDA was concerned, however, that the exposure and dose delivered in the STARS Phase 3 trial were lower than planned due to dose preparation and administration issues. Ironwood attempted to address that with a new pharmacokinetics analysis of the data, but the FDA has remained unmoved.
The company said in a statement that it is "disappointed by this outcome," but that it is now working on the design of a confirmatory phase 3 trial and regulatory path forward with the FDA.
"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," commented Ironwood's chief executive, Tom McCourt.
"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."
It's the second time in a matter of months that an SBS-IF candidate has been sent packing by the FDA. In December, the regulator issued a complete response letter (CRL) for Zealand Pharma's GLP-2 analogue glepaglutide, also asking for another phase 3 trial.
In February, Ironwood said it made $351 million in 2024 revenues from Linzess (linaclotide), its irritable bowel syndrome (IBS) and constipation therapy, and ended the year with cash reserves of almost $89 million. It expects to record Linzess sales of up to $850 million this year.
