At a Glance
- FDA accepted garetosmab BLA under Priority Review for FOP adults; decision target: August 2026.
- OPTIMA Phase 3 met primary endpoint: 94% (3 mg/kg) and 90% (10 mg/kg) reductions in new HO lesions vs. placebo.
- Post-hoc: >99% mean volume reduction of new lesions; assessed via CT, CAJIS, flare-ups.
- Favorable safety; first therapy targeting Activin A; podiatric OPTIMA 2 trial planned 2026.
Written By: Katherashala Dharan Kumar PharmD
Reviewed By: Pharmacally Editorial Team
Regeneron Pharmaceuticals announced that the FDA has accepted the Biologics License Application for garetosmab under Priority Review for treating adults with fibrodysplasia ossificans progressiva (FOP), with a decision expected by August 2026. This monoclonal antibody targets Activin A, a key protein driving heterotopic ossification (HO) in FOP. The designation highlights garetosmab’s potential to address this ultra-rare, progressive genetic condition affecting about 900 diagnosed people worldwide.
FOP causes muscles, tendons, and ligaments to turn into bone, leading to HO that restricts movement and causes skeletal deformities. Patients often face challenges like difficulty speaking, eating, walking, or breathing due to bone growth in the jaw, spine, hips, or rib cage. Most become wheelchair-bound by age 30, with median survival around 56 years; flare-ups trigger painful swelling and further progression.
OPTIMA Trial Results
The Phase 3 OPTIMA trial (NCT05394116) enrolled 63 adults with FOP, randomizing them to 3 mg/kg garetosmab, 10 mg/kg garetosmab, or placebo for 56 weeks. Disease activity was assessed via whole-body CT for HO lesions, clinician-reported flare-ups, patient assessments, CAJIS (measuring functional joint limitations; higher scores indicate greater severity), and changes in overall severity. Completers could enter an extension phase (≥84 weeks treatment) or switch to observation-only.
Both doses met the primary endpoint, reducing new HO lesions by 94% (3 mg/kg: 1 vs. 19 lesions; p=0.0274) and 90% (10 mg/kg: 2 vs. 19 lesions; p=0.0260).
Post-hoc analysis showed over 99% reduction in new lesion volume (3 mg/kg: 0.01 cm³ vs. 10.45 cm³; 10 mg/kg: 0.02 cm³ vs. 10.45 cm³).
Dose | New Lesions (vs. Placebo=19) | % Reduction | Volume Reduction (vs. Placebo=10.45 cm³) |
3 mg/kg (n=19) | 1 | 94% (p=0.0274) | >99% (0.01 cm³; p=0.0013) |
10 mg/kg (n=23) | 2 | 90% (p=0.0260) | >99% (0.02 cm³; p=0.0005) |
Safety data indicated serious adverse events in 1 (3 mg/kg), 2 (10 mg/kg), and 2 placebo patients; common reactions (≥30%) included epistaxis, increased hair growth, abscess, and acne.
Garetosmab Mechanism
Garetosmab, developed using Regeneron’s VelocImmune technology, neutralizes Activin A to prevent HO lesion formation in FOP patients. Regeneron scientists identified Activin A’s role in FOP pathology, making it a precise target. Administered intravenously every four weeks, it aims to halt abnormal bone growth without approved alternatives currently available.
Regulatory Milestones
Garetosmab holds Fast Track and Orphan Drug Designations from the FDA, plus Orphan Designation in the EU. Priority Review applies to therapies offering significant improvements for serious conditions.
A Pediatric Phase 3 trial, OPTIMA 2, is planned for later 2026. While promising, garetosmab remains investigational pending full approval.
References
Regeneron Pharmaceuticals. Garetosmab Biologics License Application Accepted for FDA Priority Review for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP). Regeneron Press Release. February 19, 2026, Garetosmab Biologics License Application Accepted for FDA Priority Review for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP) | Regeneron Pharmaceuticals Inc.
An Expanded Access Program of Garetosmab in Adult Patients With Fibrodysplasia Ossificans Progressiva (FOP), ClinicalTrials.gov ID NCT07301450, https://clinicaltrials.gov/study/NCT07301450
AstraZeneca Licenses Regeneron’s VelocImmune® Technology for Discovering Human Monoclonal Antibodies, 05 February 2026, https://investor.regeneron.com/news-releases/news-release-details/astrazeneca-licenses-regenerons-velocimmuner-technology