Richard Keen, MD, PhD, Director of the Metabolic Bone Disease Centre at the Royal National Orthopaedic Hospital in London and global principal investigator of the OPTIMA trial, discusses positive 84-week results from the phase 3 OPTIMA trial extension, evaluating Pasatru (garetosmab-grts) in adults with fibrodysplasia ossificans progressiva (FOP).
Understanding Fibrodysplasia Ossificans Progressiva
FOP is an ultra-rare genetic disorder that affects approximately 0.88 per million US residents. The condition, which is due to a mutation in the ACVR1 gene, causes progressive flare-ups with soft tissue swelling that can lead to heterotopic ossification (HO), or abnormal bone formation in muscles and other soft tissues.
As FOP progresses, abnormal bone growth restricts movement and function, which can affect a person’s ability to walk, eat, speak, and breathe. In some cases, it causes respiratory complications and premature death.
Garetosmab is a VelocImmune-derived fully human monoclonal antibody that binds to and inhibits signaling by Activin A, a protein involved in the formation of HO lesions. The drug is FDA-approved to reduce the formation of new HO lesions and clinician-assessed flare-ups in adults with FOP.
Garetosmab Demonstrates Sustained Efficacy in the Phase 3 OPTIMA Trial
Regeneron Pharmaceuticals announced positive 84-week results from its phase 3 OPTIMA trial extension (NCT05394116) evaluating garetosmab on October 12, 2026. The findings were presented at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting.
OPTIMA was a phase 3, randomized, double-blind, placebo-controlled trial enrolling 63 adults with FOP. Participants received intravenous garetosmab (10 mg/kg or 3 mg/kg) or placebo once every four weeks for 56 weeks. Fifty-eight participants completed the double-blind extension phase to at least 84 weeks.
The original 56-week trial met its primary endpoint, demonstrating a 90% or greater reduction in new HO lesions and a significant reduction in clinician-assessed flare-ups. Between weeks 56 and 84, Dr. Keen shared that researchers observed:
- No new HO lesions
No participants receiving garetosmab between weeks 56 and 84 developed new HO lesions, compared with nine new lesions among those receiving placebo, based on CT scans. In addition, one new HO lesion previously detected at week 56 for garetosmab 3 mg/kg was no longer detectable at week 84.
- Fewer clinician-assessed flare-ups
Clinician-assessed flare-ups were also less common in participants receiving garetosmab. One new flare-up was observed in the 10 mg/kg group, compared with 14 in the 3 mg/kg group, and 17 in the placebo group.
Because FOP is a progressive condition, Dr. Keen said the lack of any new HO lesions was particularly significant. These findings also suggest garetosmab offers sustained disease-modifying control.
Safety Findings and Next Steps
Both doses of garetosmab demonstrated a generally well-tolerated safety profile through week 84, consistent with findings at week 56.
Acne was the most common treatment-emergent adverse event among participants receiving the 10 mg/kg dose, while non-severe nosebleeds (epistaxis) were the most common in those receiving 3 mg/kg. Researchers also noted a dose-dependent increase in skin and soft tissue infections — 33% with placebo; 53% with garetosmab 3 mg/kg; and 78% with garetosmab 10 mg/kg. All infections resolved with further management, and none caused any participants to discontinue the treatment.
Dr. Keen shared that even though these findings are notable, continued monitoring will be necessary as garetosmab enters routine clinical practice to understand its long-term effects on patient function and safety.
Regeneron plans to begin the phase 3 OPTIMA 2 trial in children and adolescents with FOP later this year.
In Their Own Words
“The natural history of FOP is sort of a progressive, relentless deterioration over time. And I think being able to demonstrate that between week 56 and week 84 there were no new lesions seen. This demonstrates really sustained disease-modifying control…which is what patients with FOP so badly need.” – Richard Keen, MD, PhD, Director of the Metabolic Bone Disease Centre at the Royal National Orthopaedic Hospital in London and global principal investigator of the OPTIMA trial
For more information, visit: https://www.globenewswire.com/news-release/2026/10/12/3379116/0/en/pasatru-garetosmab-grts-demonstrates-zero-new-heterotopic-ossification-ho-lesions-in-adult-fibrodysplasia-ossificans-progressiva-fop-patients-during-optima-trial-extension.html
To learn more about FOP and other rare musculoskeletal diseases, visit: https://checkrare.com/diseases/musculoskeletal-diseases/