Regeneron Reports Positive Phase 3 FOP Results

Rare Daily Staff

Regeneron Pharmaceuticals said its phase 3 OPTIMA trial in adults with the ultra-rare genetic disorder fibrodysplasia ossificans progressiva met its primary endpoint by significantly reducing the number of new bone lesions.

The study showed a 90 percent or greater reduction in new bone lesions at 56 weeks, and garetosmab also led to a greater than 99 percent reduction in the total volume of new bone lesions. Based on the results and safety profile, the Independent Data Monitoring Committee recommended that those receiving placebo be transitioned to garetosmab as soon as possible. Regeneron expects to file a regulatory submission in the United States by the end of 2025.

A phase 3 trial of garetosmab in adolescents and children with FOP, OPTIMA 2, is expected to begin next year.

Fibrodysplasia ossificans progressiva is a progressive condition in which muscles, tendons, and ligaments are replaced by bone, a process known as heterotopic ossification (HO). HO of the jaw, spine, hip, and rib cage can make it difficult to speak, eat, walk, or breathe, leading to weight loss, escalating loss of mobility, and skeletal deformity. People with FOP also experience episodic, localized inflammation known as flare-ups. Most people with FOP are wheelchair-bound by 30 years old, and the median age of survival is about 56 years. Death often results from complications such as pneumonia, heart failure, and aspiration stemming from HO and loss of mobility in the chest, neck, and jaw.

Garetosmab is a monoclonal antibody that neutralizes the Activin A protein, which Regeneron scientists discovered plays a critical role in the development of bone lesions in people with FOP. The U.S. Food and Drug Administration granted Fast Track designation for garetosmab for the prevention of HO in patients with FOP. In the United States and European Union, garetosmab has also been granted Orphan Drug designation.

OPTIMA, a global, multicenter, randomized, double-blind, placebo-controlled trial, enrolled 63 people with FOP age 18 and older. Participants were randomized to receive either placebo, 3 mg/kg of garetosmab, or 10 mg/kg of garetosmab intravenously once every four weeks. Following this, participants could choose to extend treatment through at least 84 weeks or discontinue and move into an observation-only arm.

At 56 weeks, there were no discontinuations in the garetosmab groups, and there was one discontinuation in the placebo group due to an ovarian cyst. There was a dose-dependent increase in skin and soft tissue infections. There was no dose-dependent increase in nosebleeds, and there were no serious bleeding events. Musculoskeletal pain-related adverse events decreased and were similar in both garetosmab groups.

Serious treatment-emergent adverse events occurred in two patients treated with placebo, one patient treated with 3 mg/kg of garetosmab, and two patients treated with 10 mg/kg of garetosmab. No deaths were reported in the trial.

“The OPTIMA trial results clearly illustrate the potential of garetosmab to alter the disease and reduce new lesions that define this condition,” said Richard Keen, director of the Metabolic Bone Disease Centre at Royal National Orthopaedic Hospital in London and global primary investigator of the OPTIMA trial. “Notably, garetosmab is the first and only investigational therapy to demonstrate a dramatic reduction in both the number and volume of abnormal bone lesions.”