FDA Approves a Regeneron Antibody for a Rare Disease That Grows Bone in Muscle
The Food and Drug Administration has approved Pasatru, an antibody that blocks a protein called Activin A, for adults with fibrodysplasia ossificans progressiva, a disorder in which bone forms inside muscles, tendons and ligaments, Regeneron Pharmaceuticals announced Aug. 19. The approved use is to reduce the formation of new heterotopic ossification lesions, the technical name for that misplaced bone, and clinician-assessed flare-ups.
The approval rests on the Phase 3 OPTIMA trial, which enrolled 63 participants aged 18 and older, according to the company. They were randomized to Pasatru at 10 mg/kg (n=23), at 3 mg/kg (n=19) or to placebo (n=21), infused every four weeks for 56 weeks. At 56 weeks both doses met the primary endpoint: 2 new lesions on the higher dose and 1 on the lower, against 19 on placebo, counted by whole-body CT scan. Regeneron puts those at 90% and 94% reductions.
Clinician-assessed flare-ups, a key secondary endpoint, numbered 9 on the 10 mg/kg dose, 53 on 3 mg/kg and 66 on placebo, the company said. Flare-ups reported by the patients themselves did not follow: changes in the proportion of patients reporting flare-ups through week 56 "were not significantly different between placebo and Pasatru treatment groups."
Regeneron describes Pasatru as the "first and only FDA-approved treatment demonstrating reduction in new HO lesions and clinician-assessed flare-ups in a placebo-controlled trial" in adults with the disease. That is the company's own claim, and it is bounded to that pairing of endpoints and trial design.
The recommended starting dose is 10 mg/kg given intravenously over 60 minutes once a month, reducible to 3 mg/kg if not tolerated. The label warns the drug can harm a fetus and must not be used in pregnancy, and flags skin and soft-tissue infections and serious nosebleeds. Serious treatment-emergent adverse events occurred in two patients on 10 mg/kg, one on 3 mg/kg and two on placebo.
About 900 people worldwide are diagnosed with the disorder, and most use a wheelchair by age 30.
