Regeneron is racing to regulators after reporting a phase 3 win in an ultrarare disease. The biotech plans to file for FDA approval of garetosmab in fibrodysplasia ossificans progressiva (FOP) by the end of 2025 on the strength of a pivotal trial that read out on Wednesday.
The study randomized 63 adults with FOP to receive one of two doses of the anti-activin A antibody garetosmab or placebo every four weeks for 56 weeks. At the end of the trial, there were one and two new abnormal bone lesions, respectively, in patients on the low and high doses of garetosmab. Regeneron reported 19 new lesions in the placebo group.
With a 90% or greater reduction in lesions in both treatment arms, the study met its primary endpoint. The outcome supports Regeneron’s findings that the activin A protein is critical to the development of heterotopic ossification lesions, deposits of bone in soft tissues that define FOP.
Regeneron named clinician-assessed flare-ups, a term for cases of episodic, localized inflammation, as a key secondary endpoint. There were 70 flare-ups in the placebo arm, compared to 53 cases on the low dose of garetosmab. That 20% reduction wasn’t statistically significant. But the high dose performed better, with nine flare-ups and a statistically significant 89% reduction compared to placebo.
Nobody on garetosmab stopped treatment and there was no dose-dependent increase in nosebleeds, a side effect seen in a phase 2 trial of the antibody. There were no serious bleeding events and no deaths.
Safety was a key area of focus. When Regeneron reported phase 2 data in 2020, the company planned to seek FDA approval early the following year. However, the company paused the study later in 2020 after multiple patients died in the extension part of the trial.
Five out of 44 patients died. Researchers said the events were unlikely to be related, noting that there was no clear pattern to link the deaths to the treatment or to the mechanism of action, but were unable to rule out a causal connection to garetosmab. Regeneron dropped garetosmab from its list of planned FDA filings for the year partway through 2021.
Based on the phase 3 results, the Independent Data Monitoring Committee recommended switching patients on placebo to garetosmab as soon as possible. Regeneron is moving quickly, too, with a filing for FDA approval planned for this year and global submissions on the schedule for 2026. The company plans to start a phase 3 trial in adolescents and children with FOP next year.
Ipsen won FDA approval for Sohonos in adults and children with FOP in 2023. However, after a troubled development, the drug has underperformed commercially. Ipsen took (PDF) an impairment loss of 279 million euros ($330 million) related to the product. Sohonos sales fell (PDF) 20% to 8.3 million euros in the first half of 2025.
The French drugmaker is developing a next-generation FOP drug, fidrisertib. Data from a registrational phase 2 trial of the candidate are expected this year. Ipsen has enrolled children as young as five years in the study and expects fidrisertib to be free from some of the safety problems that have impeded sales of Sohonos.