Stopping Bone from Regrowing in Soft Tissue: FDA Approves FOP Antibody Drug Pasatru

For patients with fibrodysplasia ossificans progressiva (FOP), the challenge is not merely abnormal bone growth, but the gradual invasion of muscles, tendons, and ligaments by bone tissue. New bone masses may lock joints and restrict eating, walking, and even breathing. The U.S. Food and Drug Administration (FDA) has now approved Regeneron’s garetosmab, marketed as Pasatru, for the treatment of adults with FOP, adding an entirely new antibody therapy aimed at stopping this pathological process.

FOP is usually associated with variants in the ACVR1 gene, causing Activin A, which normally participates in tissue signaling, to abnormally drive bone formation. Garetosmab is an intravenously administered monoclonal antibody that neutralizes Activin A in an attempt to interrupt the signal before heterotopic bone forms in soft tissue, rather than removing bone masses that have already developed.

The approval was based on the Phase 3 OPTIMA trial, which enrolled 63 adults and used a randomized, placebo-controlled, multiple-blind design. Participants received 3 mg/kg or 10 mg/kg of garetosmab, or placebo, every four weeks for 56 weeks. Trial registration data indicate that the primary assessments included the number of new heterotopic bone lesions and the incidence and severity of adverse events during a specified treatment period.

At 56 weeks, the low-dose group had a total of 1 new lesion, the high-dose group had 2, and the placebo group had 19, corresponding to reductions of 94% and 90%, respectively. A post hoc analysis of lesion volume also showed reductions of more than 99% in both dose groups compared with placebo. These results provide direct randomized controlled evidence that inhibiting Activin A can indeed reduce new heterotopic bone formation.

Safety remains an important consideration for long-term treatment. During the 56 weeks, 5 of the 63 participants experienced serious treatment-emergent adverse events, distributed across the two treatment groups and the placebo group; no deaths were reported. Data presented at a meeting showed that skin and soft-tissue infections were more common in the treatment groups, including acne, folliculitis, abscesses, and cellulitis. Reactions such as nosebleeds and increased hair growth also require continued monitoring.

Background

Pasatru is not the first FOP drug in the United States. In 2023, the FDA approved the oral drug Sohonos (palovarotene) for adults and children who have reached specified ages to reduce the volume of new heterotopic bone. The two treatments differ in their mechanisms of action, routes of administration, and study designs; Pasatru’s important added value is that a placebo-controlled trial demonstrated that an Activin A antibody can reduce both the number and volume of new lesions in adults.

However, OPTIMA included only 63 people and enrolled adults with disease activity or lesion progression. Existing publicly available data remain insufficient to determine whether reductions in lesions on imaging will translate years later into better mobility, respiratory function, or quality of life. Regeneron plans to launch a Phase 3 study in children and adolescents later in 2026. Whether the eligible age range can be expanded will depend on efficacy, safety, and long-term follow-up results in the pediatric population.