FDA starts review of Regeneron's drug for rare disease FOP

Patients in the US with rare bone disease fibrodysplasia ossificans progressiva (FOP) could have a second treatment option in a matter of months, if the FDA clears a just-filed marketing application for Regeneron's garetosmab therapy.

The regulator has started a priority review of the anti-activin A antibody, with a decision due in August, based on the results of the phase 3 OPTIMA trial involving 63 patients with FOP, a life-shortening and highly debilitating disorder in which bony lesions – known as heterotopic ossifications (HO) – are laid down in muscles, tendons, and ligaments.

If approved, garetosmab will be the first alternative to Ipsen's oral RAR gamma agonist Sohonos (palovarotene), which was approved by the FDA for FOP in 2023 but has failed to live up to its commercial promise.

Ipsen reported full-year sales of the drug last year of €20.7 million ($24.3 million), compared to €20.8 million in the previous year, and said it was taking an impairment charge on its books of around €257 million, mainly driven by Sohonos' stalled uptake.

Regeneron said it has high hopes for garetosmab because, if approved, it will be "the first and only available treatment shown to reduce the number and volume of new heterotopic bone lesions in adults with FOP."

According to the company, approximately 900 people are diagnosed with FOP worldwide, including around 400 in the US, with many others believed to be undiagnosed or misdiagnosed. Most people with FOP are wheelchair bound by 30 years old, and the median age of survival is just 56 years.

In OPTIMA, patients were randomised to one of two doses of garetosmab (3 mg/kg or 10 mg/kg), given by intravenous infusion every four weeks, or a matched placebo. The primary endpoint of the trial was the reduction in new HO lesions at 56 weeks, which was reduced by 94% with the lower dose and 90% with the higher dose compared to the control group.

Both doses of garetosmab also demonstrated a greater than 99% reduction in the mean total volume of new HO lesions.

Regeneron is now preparing for additional regulatory filings for garetosmab in FOP and has indicated it plans to double down on its investment in the programme with the start later this year of a second phase 3 trial, OPTIMA 2, that will recruit children and adolescents with FOP.

Ipsen was also developing a second FOP candidate, fidrisertib, in the pivotal FALKON trial, but that did not meet its primary endpoint, and the programme no longer appears in its R&D pipeline listing.