FDA Approves Activin Signaling Inhibitor for Bone Disorder

The FDA recently approved garetosmab (Pasatru) for use in adults with fibrodysplasia ossificans progressiva (FOP), an ultra-rare progressive bone disorder. This monoclonal antibody functions by binding to and neutralizing activin A, a protein involved in the formation of heterotopic bone growth in FOP patients. FOP primarily affects fewer than 500 people in the U.S., causing rapid bone growth that infiltrates muscles, tendons, and ligaments, severely limiting mobility and independence.

OPTIMA, a phase III trial with 63 participants, provided support for garetosmab's approval. At 56 weeks, two dosages administered every four weeks demonstrated a 90-94% reduction in new heterotopic ossification lesions, as detected by low-dose CT scans. The intravenous drug was also associated with a significant reduction in disease flares, with an 88% decrease at the 10 mg/kg dose and a 15% reduction at the 3 mg/kg dose.

FOP's frequent bone growth can lead to life-threatening complications, such as breathing problems from rib cage bone growth and cardiorespiratory failure. Dr. Kathryn Dahir, an endocrinologist at Vanderbilt University, highlighted that garetosmab's ability to reduce new bone formations and flares offers a newfound treatment option for FOP patients. This IV-administered drug is only the second to be approved for FOP, following the 2023 approval of oral retinoid palovarotene, which is also indicated for children.

Side effects of garetosmab include epistaxis, abscess, acne, increased hair growth, madarosis, oral ulcers, folliculitis, paronychia, rash, and embryo-fetal toxicity, skin and soft tissue infections, as well as serious nose bleeds. The recommended dosage is 10 mg/kg every four weeks, but it can be reduced to 3 mg/kg if tolerability is a concern.