FDA Grants Priority Review to Regeneron's Garetosmab for Rare Bone Disease FOP

The U.S. Food and Drug Administration has accepted Regeneron Pharmaceuticals' Biologics License Application for priority review of garetosmab, a treatment for adults with fibrodysplasia ossificans progressiva (FOP). The FDA's target decision date is set for August 2026.

If approved, garetosmab would become the first available treatment shown to reduce both the number and volume of new heterotopic bone lesions in adults with FOP. The monoclonal antibody works by blocking Activin A, a protein that Regeneron scientists identified as critical in the development of heterotopic ossification in FOP patients.

FOP is an ultra-rare genetic disorder where abnormal bone forms in muscles and other connective tissues, causing progressive disability. The disorder is life-shortening and highly debilitating, with bony lesions known as heterotopic ossifications laid down in muscles, tendons, and ligaments. Most people with FOP are wheelchair-bound by age 30, with a median survival age of approximately 56 years.

The application is supported by data from the Phase 3 OPTIMA trial, which involved 63 patients with FOP. 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 heterotopic ossification lesions at 56 weeks.

Patients receiving the 3 mg/kg dose experienced a 94% reduction in new lesions, while those on the 10 mg/kg dose saw a 90% reduction compared to the control group. A post-hoc analysis showed both doses reduced the mean total volume of new lesions by more than 99% compared to placebo.

The most common adverse reactions included epistaxis, increased hair growth, abscess and acne. Serious treatment-emergent adverse events occurred in one patient on the lower dose, two patients on the higher dose, and two patients on placebo.

FOP affects approximately 900 diagnosed people worldwide, including around 400 in the US, with many others believed to be undiagnosed or misdiagnosed. 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. Ipsen reported full-year sales of Sohonos 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 is now preparing for additional regulatory filings for garetosmab in FOP and has indicated it plans to start later this year a second phase 3 trial, OPTIMA 2, that will recruit children and adolescents with FOP. The FDA previously granted Fast Track designation and Orphan Drug Designation for garetosmab.