What did the phase 3 OPTIMA trial show?
OPTIMA (NCT05394116) enrolled 63 adults with any FOP-causing variant of type I Activin A receptor (ACVR1) who exhibited disease activity or HO lesion progression.¹,² At 56 weeks, garetosmab 10 mg/kg (n=23) and 3 mg/kg (n=19) both met the primary endpoint, reducing new HO lesions by 90% (2 lesions versus 19) and 94% (1 lesion versus 19) compared with placebo (n=21), as assessed by CT scan.¹
Clinician-assessed flare-ups, a key secondary endpoint, were reduced 88% with the 10 mg/kg dose (9 flare-ups) and 15% with the 3 mg/kg dose (53 flare-ups) compared with 66 flare-ups on placebo; patient-reported flare-up rates did not differ significantly between groups.¹ Serious treatment-emergent adverse events occurred in 2 patients on 10 mg/kg garetosmab, 1 on 3 mg/kg, and 2 on placebo. Common adverse reactions in at least 10% of treated patients included abscess, acne, increased hair growth, madarosis, oral ulcers, epistaxis, folliculitis, paronychia, and rash.¹ Following the initial 56-week period, participants could elect to continue their originally assigned treatment in a double-blind extension phase for at least 84 weeks or enter an observation-only arm.¹
How does garetosmab work?
Garetosmab is a VelocImmune-derived, fully human monoclonal antibody that binds and neutralizes Activin A, a protein Regeneron scientists identified as critical to HO lesion development in FOP.¹ It is dosed intravenously over 60 minutes once every 4 weeks, starting at 10 mg/kg by weight, with a reduction to 3 mg/kg if not tolerated, and can be administered across care settings including home infusion.¹ In an earlier phase 2 trial, garetosmab was associated with adverse events including epistaxis, madarosis, and skin abscesses, consistent with the safety profile now reflected in its approved label.³
What's next for garetosmab?
A regulatory submission for garetosmab is under review by the European Medicines Agency, with additional submissions planned in other countries, including Japan. The therapeutic previously received FDA fast track and orphan drug designations, plus orphan designations from European Union and Japanese regulators.¹ A phase 3 trial in adolescents and children with FOP, OPTIMA 2, is planned to begin later this year.
Garetosmab was developed using Regeneron's VelocImmune platform, which has also produced several other FDA-approved human monoclonal antibodies. Regeneron's myRARE program offers patients and health care providers resources including product information, insurance benefit verification, and information about potential financial support.¹
References
- Regeneron Pharmaceuticals. Pasatru (garetosmab-grts) first and only FDA-approved treatment demonstrating reduction in new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in a placebo-controlled trial in adults with fibrodysplasia ossificans progressiva (FOP). Press release. Published August 19, 2026. Accessed August 20, 2026. https://investor.regeneron.com/news-releases/news-release-details/pasatrutm-garetosmab-grts-first-and-only-fda-approved-treatment
- ClinicalTrials.gov. A study to assess safety, tolerability and efficacy of garetosmab versus placebo administered intravenously (IV) in adult participants with fibrodysplasia ossificans progressiva (FOP) (OPTIMA). NCT05394116. Updated July 17, 2026. Accessed August 20, 2026. https://clinicaltrials.gov/study/NCT05394116
- Di Rocco M, Forleo-Neto E, Pignolo RJ, et al. Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial. Nat Med. 2023;29(10):2615-2624. doi:10.1038/s41591-023-02561-8