FDA Approves Activin Signaling Inhibitor for Bone Disorder

The FDA approved garetosmab (Pasatru) to reduce the formation of new heterotopic ossification lesions and disease flares in adults with fibrodysplasia ossificans progressiva (FOP), the agency announced on Wednesday.

A monoclonal antibody, garetosmab works by binding to and neutralizing activin A, a protein that plays a key role in the development of heterotopic bone growth in patients with the ultra-rare progressive disease.

FOP is caused by a mutation in activin A receptor-type 1 and is estimated to affect fewer than 500 people in the U.S. It is characterized by episodes of rapid bone growth that infiltrates muscles, tendons, and ligaments and seriously impedes patients’ mobility and daily function, including their ability to eat, drink, or use the restroom independently.

Most patients need a wheelchair by the age of 30, and the disease can significantly shorten lives. Bone growth around the rib cage, for example, can result in breathing problems and cardiorespiratory failure.

Garetosmab’s approval was supported by OPTIMA, a 63-patient phase III trial. At 56 weeks, the placebo-controlled study showed that two different dosages of garetosmab every 4 weeks led to a 90-94% reduction in the number of new heterotopic ossification lesions, as shown on low-dose CT scans. Delivered intravenously, garetosmab was also associated with fewer investigator-assessed disease flares, with an 88% reduction versus placebo at the 10 mg/kg dose and a 15% reduction at the 3 mg/kg dose.

“For people living with FOP, every irregular new bone formation is a step toward disability and potential loss of mobility,” said investigator Kathryn Dahir, MD, an endocrinologist at Vanderbilt University in Nashville, Tennessee, in a press release from drugmaker Regeneron. “With the ability to reduce the number of new bone lesions and flare-ups, we now have a new treatment that can positively affect patients.”

The IV-administered drug is just the second to be approved for FOP, following the 2023 approval of the oral retinoid palovarotene (Sohonos), which carries an indication for kids as well. A planned phase III trial (OPTIMA-2) will soon test garetosmab in children and adolescents.

Common adverse events in OPTIMA (occurring in at least 10% of participants) included epistaxis, abscess, acne, increased hair growth, madarosis, oral ulcers, folliculitis, paronychia, and rash.

The warnings and precautions section of the labeling includes risk of embryo-fetal toxicity, skin and soft tissue infections, and serious nose bleeds.

According to the prescribing information, the recommended dose of garetosmab is 10 mg/kg every 4 weeks, but the dosage can be decreased to 3 mg/kg if tolerability is an issue.