The US FDA has approved Pasatru (garetosmab-grts), a fully human anti-Activin A monoclonal antibody developed by Regeneron Pharmaceuticals (Nasdaq: REGN), to reduce the formation of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva (FOP). The approval marks only the second treatment authorized for this ultra-rare condition, which affects approximately 900 people worldwide, and the first to demonstrate HO lesion reduction in a placebo-controlled trial.
Pasatru is administered intravenously over 60 minutes once monthly, with a recommended starting dose of 10 mg/kg that may be reduced to 3 mg/kg if not tolerated. It can be given across care settings, including home infusion. The drug carries contraindications in pregnancy and warnings regarding serious skin infections and nosebleeds.
The approval was supported by the Phase III OPTIMA trial, a multicenter, multinational, randomized, placebo-controlled study enrolling 63 adults with FOP-causing ACVR1 variants. At 56 weeks, both doses met the primary endpoint: the 10 mg/kg arm recorded 2 new HO lesions versus 19 in the placebo group (90% reduction), and the 3 mg/kg arm recorded 1 lesion versus 19 (94% reduction), as assessed by computed tomography scan. Clinician-assessed flare-ups, a key secondary endpoint, were reduced by 88% in the 10 mg/kg arm relative to placebo, though patient-reported flare-up differences were not statistically significant between groups. As previously reported, the biologics license application had received Priority Review with a target action date of August 2026.
Garetosmab-grts neutralizes Activin A, a TGF-β superfamily ligand that Regeneron scientists identified as driving aberrant osteogenic signaling through gain-of-function ACVR1 mutations characteristic of FOP. By blocking Activin A in the extracellular space, the antibody interrupts downstream SMAD1/5/8 phosphorylation and ectopic bone formation in soft tissues. The molecule was generated using Regeneron's VelocImmune platform, which has now produced multiple FDA-approved fully human antibodies.