Efficacy and safety of garetosmab, an activin A-blocking antibody, in fibrodysplasia ossificans progressiva (OPTIMA): a randomised, double-blind, placebo-controlled, phase 3 trial.
Riccardo Papa, Susan Rhee, Patricia Delai et al.
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In 30 seconds
OPTIMA was a multicentre, randomised, double-blind, placebo-controlled phase 3 trial assessing monthly intravenous garetosmab in adults with fibrodysplasia ossificans progressiva. Among 63 participants, the total number of new heterotopic bone lesions by week 56 was 19 with placebo, compared with one with garetosmab 3 mg/kg and two with 10 mg/kg. Both doses significantly reduced lesion counts versus placebo. Treatment-emergent adverse events of special interest occurred in 0, 1, and 4 participants in the 3 mg/kg, placebo, and 10 mg/kg groups, respectively; all were considered treatment-related, and no deaths occurred.
Key findings
- At week 56, new heterotopic bone lesions numbered 19 with placebo, one with garetosmab 3 mg/kg, and two with 10 mg/kg.
- Compared with placebo, lesion rate ratios were 0·06 (95% CI 0·00-0·73; p=0·027) for 3 mg/kg and 0·10 (0·01-0·76; p=0·026) for 10 mg/kg.
- Treatment-emergent adverse events of special interest occurred in one (5%) placebo recipient, zero receiving 3 mg/kg, and four (17%) receiving 10 mg/kg; all were considered treatment-related.
Why it matters
FOP causes progressive heterotopic bone formation and substantial disability. This placebo-controlled phase 3 trial provides evidence that blocking activin A can markedly reduce new lesion formation in adults with the disorder, while also documenting treatment-related adverse events, particularly in the higher-dose group. These findings inform assessment of a potential disease-modifying approach in a condition with serious progressive consequences.
What to keep in mind
The trial included 63 participants, reflecting the ultrarare condition, and reports the primary endpoint at week 56; longer-term effects and safety are not established by these results.