The U.S. Food and Drug Administration (FDA) has approved Pasatru (garetosmab-grts) as a treatment for adults with fibrodysplasia ossificans progressiva (FOP), an extremely rare genetic disorder in which muscles, tendons and ligaments can gradually turn into bone. The approval makes Pasatru the second FDA-approved treatment for FOP, providing another therapeutic option for people affected by this debilitating condition.
FOP is caused by mutations in the ACVR1 gene, which plays an important role in regulating bone formation. In people with FOP, abnormal signaling through this pathway can cause bone to form in soft tissues where bone normally should not develop. This process, known as heterotopic ossification, can progressively restrict movement, cause severe disability and contribute to the formation of what is sometimes described as a “second skeleton.”
Pasatru is an antibody designed to target the abnormal signaling pathway involved in FOP. By blocking activation of the activin A receptor type 1 pathway, the medicine is intended to reduce the formation of new abnormal bone and decrease disease flare-ups.
The FDA's approval was supported by a randomized, double-blind, placebo-controlled clinical study involving 63 adults with FOP. Participants received Pasatru at doses of 3 mg/kg or 10 mg/kg, or placebo, through intravenous infusion every four weeks for 56 weeks. During the study, patients receiving the 10 mg/kg dose experienced substantially fewer new heterotopic ossification lesions compared with those receiving placebo.
The clinical study also showed a reduction in disease flare-ups. During the 56-week treatment period, there were 9 flare-ups among patients receiving 10 mg/kg Pasatru, compared with 53 among those receiving 3 mg/kg and 66 in the placebo group. These findings supported the medicine's effectiveness in reducing disease activity associated with FOP.
The recommended starting dose of Pasatru is 10 mg/kg administered intravenously over 60 minutes once every four weeks. If the 10 mg/kg dose is not tolerated, the dose may be reduced to 3 mg/kg once every four weeks.
The FDA has also highlighted important safety considerations. Pasatru carries a warning regarding potential fetal harm, and patients who can become pregnant should use effective contraception during treatment and for six months after the final dose. The medicine also carries warnings concerning skin and soft-tissue infections and nosebleeds that may require medical treatment. Common adverse reactions reported with treatment include nosebleeds, increased hair growth, abscesses and acne.
The approval marks another important development in the treatment of FOP. In 2023, the FDA approved Sohonos (palovarotene) as the first treatment for FOP. Pasatru therefore becomes the second approved therapy for this exceptionally rare disease.
Pasatru received several FDA development designations, including Breakthrough Therapy, Fast Track, Orphan Drug and Priority Review. The approval was granted to Regeneron Pharmaceuticals, Inc.
For people living with FOP, the availability of a second approved treatment represents an important expansion of therapeutic options and could help reduce the abnormal bone formation and painful disease flare-ups associated with this rare genetic disorder.
