Regeneron Pharmaceuticals has reported positive results from its Phase 3 OPTIMA trial evaluating garetosmab in adults with fibrodysplasia ossificans progressiva (FOP), an ultra-rare genetic disorder where muscles, tendons, and ligaments are progressively replaced by bone. This condition can lead to severe loss of mobility and other serious complications.
Garetosmab, a monoclonal antibody that targets the Activin A protein implicated in FOP, is the first treatment to show a significant reduction in both the number and volume of abnormal bone lesions in affected adults. The primary endpoint was met, demonstrating at least a 90% reduction in new heterotopic ossification (HO) lesions at 56 weeks. According to Regeneron, there was also a greater than 99% reduction in the total volume of new HO lesions among those treated with garetosmab compared to placebo.
“Heterotopic ossification is a hallmark of FOP, a horrific disease in which muscles, tendons and ligaments are progressively replaced by bone, gradually incapacitating patients,” said Professor Richard Keen, Director of the Metabolic Bone Disease Centre at the Royal National Orthopaedic Hospital in London and global primary investigator of the OPTIMA trial. “The OPTIMA trial results clearly illustrate the potential of garetosmab to alter the disease and reduce new lesions that define this condition. Notably, garetosmab is the first and only investigational therapy to demonstrate a dramatic reduction in both the number and volume of abnormal bone lesions.”
The randomized double-blind study enrolled 63 adults with FOP across multiple international centers. Participants received either placebo or one of two doses of garetosmab every four weeks for 56 weeks. Results showed that those receiving garetosmab had markedly fewer new HO lesions than those on placebo: a 94% reduction with 3 mg/kg dose and a 90% reduction with 10 mg/kg dose. Post-hoc analysis revealed nearly complete suppression—over 99%—of total new lesion volume compared to placebo.
Safety findings indicated no discontinuations among patients on garetosmab during the study period; one patient discontinued from the placebo group due to an unrelated medical issue. There were some dose-dependent increases in skin and soft tissue infections but no serious bleeding events or deaths reported.
“The success of the OPTIMA trial is a direct result of Regeneron’s relentless pursuit of science and use of proprietary technologies to improve the lives of people with debilitating and life-threatening diseases, no matter their prevalence,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron. “Our research in FOP began decades ago – leading to the discovery of the role Activin A plays in driving this devastating disease, and now, a medicine with the potential to prevent the uncontrolled formation of new bone. We are thankful to the many patients, healthcare providers, and others who have been active partners on this journey, and we look forward to submitting garetosmab for evaluation by regulatory authorities as soon as possible.”
Following review by an independent data monitoring committee (IDMC), it was recommended that all participants receiving placebo be switched over to garetosmab treatment as soon as possible based on these efficacy data.
A U.S. regulatory submission for garetosmab is planned for late 2025; global submissions are expected next year. An additional Phase 3 trial investigating use in adolescents and children (OPTIMA 2) is planned.
FOP affects about 900 people worldwide but may be underdiagnosed due to its rarity and complexity.
Garetosmab was created using Regeneron’s VelocImmune technology platform—a system that enables development of fully human monoclonal antibodies through genetically engineered mice models—and has previously received Fast Track designation from U.S. regulators for prevention of HO in FOP patients.
For more information about ongoing clinical trials or participation details regarding OPTIMA or future studies involving garetosmab visit https://investor.regeneron.com or contact clinicaltrials@regeneron.com.
