Regeneron Pharmaceuticals has won FDA approval for Pasatru, or garetosmab-grts, to reduce new heterotopic ossification lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder marked by abnormal bone formation.
Pasatru is a fully human monoclonal antibody that blocks Activin A, a protein Regeneron identified as critical to the development of heterotopic ossification, or HO, in people with FOP. The company said it is the first and only FDA-approved treatment to demonstrate reductions in both new HO lesions and clinician-assessed flare-ups in a placebo-controlled trial in adults with the disease.
FOP causes bone to form progressively in muscles, tendons, ligaments and other connective tissues. The condition can affect the jaw, spine, hips and rib cage, making speaking, eating, walking and breathing increasingly difficult. About 900 people worldwide are diagnosed with FOP, and most patients use wheelchairs by age 30, according to Regeneron.
The approval was based on the Phase 3 OPTIMA trial, which enrolled 63 adults with active FOP. Participants received intravenous Pasatru at 10 mg/kg, Pasatru at 3 mg/kg, or placebo once every four weeks for 56 weeks.
Both Pasatru doses met the trial’s primary endpoint. Computed-tomography scans found two new HO lesions in the 10 mg/kg group and one lesion in the 3 mg/kg group, compared with 19 lesions in the placebo group. That represented reductions of 90% and 94%, respectively.
Clinician-assessed flare-ups totaled nine in the 10 mg/kg group, 53 in the 3 mg/kg group and 66 among placebo recipients. Patient-reported flare-ups were not significantly different between the placebo and Pasatru groups through week 56.
The recommended starting dose is 10 mg/kg, administered intravenously over 60 minutes every four weeks. The dose may be reduced to 3 mg/kg if the higher dose is not tolerated. The therapy may be administered in several care settings, including home infusion when appropriate.
Pasatru carries warnings including a risk of serious fetal harm, skin and soft-tissue infections, and nosebleeds. Common adverse reactions include abscesses, acne, increased hair growth, loss of eyebrows or eyelashes, mouth ulcers, nosebleeds, folliculitis, nail infections and rash.
Regeneron said an EU submission is under review, additional filings are planned, and a Phase 3 trial in adolescents and children is expected to begin later this year.
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