Ipsen’s oral small molecule has failed to reduce the progression of a genetic disease that gradually turns tendons and ligaments into bone, prompting the pharma to stop the study early.
The pivotal phase 2 miss was reported in a Dec. 19 release, though the French drugmaker did not disclose any data behind the news.
Known as FALKON, the study launched in 2021 and enrolled 113 adults and children with fibrodysplasia ossificans progressiva (FOP), a rare connective tissue disorder. The trial was evaluating Ipsen’s fidrisertib and had a primary readout slated for 2029, according to ClinicalTrials.gov.
FALKON failed to fly above the study’s main measure, which was reducing new heterotopic ossifications—the process that leads to bone formation in connective tissues—compared to placebo. Once formed, they cannot be reversed.
As a result, Ipsen is shuttering the pivotal, three-part study. In the first phase, patients received either high or low doses of fidrisertib based on weight or a placebo. The primary measure was yearly changes from baseline in ossification volume.
The second part randomized the patients that had initially received a placebo to receive either high- or low-dose fidrisertib. The final portion was an extension for participants responding to treatment.
The experimental small molecule was generally well tolerated with no reported safety concerns, according to Ipsen.
“These results are disappointing for the [FOP] community and patients living with this devastating disease,” Ipsen R&D head and Executive Vice President Christelle Huguet, Ph.D., said in the release. “However, we do believe that these data will contribute to the growing body of research on FOP, giving new insights into managing this disease for patients and their care providers.”
People living with the condition have an average life expectancy of 56 years, with the bone formations around the rib cage leading to breathing problems. About 900 people have been diagnosed with the condition across the world.
Treatment options are extremely limited. In 2023, Ipsen won an FDA approval in FOP for the retinoid therapy Sohonos. However, the drug—which carries a boxed warning—has underperformed commercially, with sales falling (PDF) 20% to 8.3 million euros in the first half of 2025.
The French drugmaker pinned its hopes on fidrisertib, hoping the next-gen drug would be free of the safety problems that impeded Sohonos sales.
Fidrisertib is designed to inhibit pathogenic variants of the ALK2 kinase, which is the underlying cause of most cases. The FALKON study enrolled patients with a R206H ACVR1 mutation or other variants of the condition that are associated with progressive ossifications.
Ipsen’s trial miss follows a phase 3 success from Regeneron in the same indication. Based on the results, Regeneron said in September that it planned to file for the FDA's approval of its drug—dubbed garetosmab— by the end of 2025.
Garetosmab is an anti-activin A antibody that was tied to a 90% or greater reduction in new abnormal bone lesions. The outcome supports Regeneron’s findings that activin A is crucial in the development of heterotopic ossifications.
But Regeneron’s journey was anything but smooth. After reporting phase 2 data in 2020, the company planned to seek FDA approval early the following year. However, Regeneron paused the study later in 2020 after multiple patients died in an extension part of the trial.
Ultimately, researchers said the deaths were unlikely to be related, noting that there was no clear pattern to link the events to the treatment or to the mechanism of action, but were unable to rule out a causal connection to garetosmab.