FDA approved garetosmab for adults with FOP after phase 3 data showed fewer new HO lesions and clinician-assessed flare-ups vs placebo.
The FDA has approved garetosmab-grts (Pasatru), an intravenous activin A–neutralizing monoclonal antibody, to reduce new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva (FOP). The decision was supported by the placebo-controlled, phase 3 OPTIMA trial, according to an August 19 announcement from Regeneron Pharmaceuticals.¹
“For people living with FOP, every irregular new bone formation is a step toward disability and potential loss of mobility,” said Kathryn Dahir, MD, professor of medicine at Vanderbilt University and a primary OPTIMA investigator. She added that reducing new lesions and flare-ups provides another treatment option for affected adults.¹
FOP is an ultra-rare genetic disorder characterized by progressive bone formation within muscles, tendons, ligaments, and other connective tissues. HO involving the jaw, spine, hips, or rib cage can impair eating, speaking, ambulation, and breathing. Regeneron estimated that approximately 900 individuals worldwide have a confirmed diagnosis, although the announcement did not describe how that estimate was derived.¹
OPTIMA enrolled 63 adults with an FOP-causing variant in the activin A receptor type 1 gene (ACVR1), evidence of disease activity or HO progression, and a cumulative analogue joint involvement scale score of 19 or lower. Participants were randomly assigned to intravenous garetosmab 10 mg/kg, garetosmab 3 mg/kg, or placebo every 4 weeks for 56 weeks. Whole-body computed tomography was used to identify new HO lesions. Additional assessments included clinician- and patient-reported flare-ups, joint involvement, disease severity, and safety.¹
At week 56, investigators counted 2 new lesions in the 10-mg/kg group, 1 in the 3-mg/kg group, and 19 in the placebo group, corresponding to reported reductions of 90% and 94%, respectively, vs placebo. Clinicians documented 9 flare-ups with 10 mg/kg, 53 with 3 mg/kg, and 66 with placebo. However, differences in patient-reported flare-ups were not statistically significant.¹
Serious treatment-emergent adverse events occurred in 2 of 23 participants receiving 10 mg/kg, 1 of 19 receiving 3 mg/kg, and 2 of 21 receiving placebo. Adverse reactions reported in at least 10% of garetosmab-treated participants included abscess, acne, increased hair growth, madarosis, oral ulcers, epistaxis, folliculitis, paronychia, and rash. The prescribing safety information warns of embryo-fetal harm, skin and soft-tissue infections, and potentially serious epistaxis. Garetosmab is contraindicated during pregnancy.¹
Garetosmab binds and neutralizes activin A, which is implicated in ACVR1-mediated heterotopic bone formation in FOP. The recommended starting dose is 10 mg/kg infused over 60 minutes every 4 weeks; the dose may be reduced to 3 mg/kg if the higher dose is not tolerated.¹
The lesion findings establish biological activity over 56 weeks, but their implications for long-term mobility, respiratory function, pain, and independence remain uncertain. Interpretation is also limited by the small sample, restriction to adults with active disease and specified baseline joint involvement, and discordance between clinician- and patient-assessed flare-ups. The source did not provide comparative evidence against other FOP therapies or guideline-based treatment strategies.
An extension is evaluating longer exposure, and the company plans the phase 3 OPTIMA 2 trial in adolescents and children. A European Medicines Agency review is ongoing; submissions in Japan and other countries are planned.¹
