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Ironwood Pharmaceuticals is working with Goldman Sachs to evaluate “strategic alternatives” after a major regulatory setback derailed its plans to bring its lead drug candidate apraglutide to market.
The move follows a 32% drop in Ironwood’s share price on 14 April, when the company disclosed that the US Food and Drug Administration (FDA) is requiring a new Phase III trial for apraglutide, its treatment for short bowel syndrome with intestinal failure (SBS-IF).
The decision raises questions about the company’s future direction. Just months ago, Ironwood made sweeping internal changes – cutting approximately half of its workforce, shelving a Phase II study of apraglutide in graft-versus-host disease (GvHD), and scaling back investment in its marketed drug Linzess (linaclotide) – to concentrate resources on bringing apraglutide to market.
Apraglutide, a long-acting synthetic glucagon-like peptide 2 (GLP-2) analogue, was acquired in Ironwood’s $1bn purchase of VectivBio in December 2023. At the time, Ironwood described the deal as a way to “strengthen its gastrointestinal pipeline”, with expectations that the commercialisation of apraglutide could begin impacting earnings per share by early 2026.
However, in February 2024, the company’s stock took a hit after apraglutide showed mixed efficacy results in the Phase III STARS trial (NCT04627025).
In its announcement earlier this month, Ironwood said that while preparing its regulatory submission, “pharmacokinetic analysis indicated that the exposure and dose delivered in the STARS Phase III trial were lower than planned due to dose preparation and administration”.
The company had believed the existing data – combined with positive long-term extension results showing 27 patients achieved enteral autonomy – could support approval.
Ironwood initiated a rolling new drug application (NDA) submission this year, with plans to complete the filing in Q3. However, after discussions with the FDA, the agency made clear that a confirmatory Phase III trial would be necessary to proceed, pushing back any potential approval by several years.
Ironwood CEO Tom McCourt said: “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 III trial.
“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.”
GlobalData’s Pharma Intelligence Center forecasts that apraglutide has the potential to generate up to $586m in global sales by 2030.