Garetosmab (Pasatru) sharply reduces new bone lesions in adults with FOP, phase 3 Lancet trial shows; FDA approved Aug. 19, 2026

A phase 3 trial published in The Lancet found that garetosmab sharply reduced new abnormal bone lesions in adults with fibrodysplasia ossificans progressiva, or FOP, providing peer-reviewed evidence for a newly approved treatment in one of medicine’s rarest and most disabling genetic diseases.

FOP is an ultra-rare disorder in which connective tissues such as muscle, tendons and ligaments progressively turn into bone outside the normal skeleton, a process known as heterotopic ossification. The disease causes severe loss of mobility and other complications, and preventing each new bone lesion matters because the changes are cumulative and can permanently restrict movement. FOP affects an estimated 1 to 2 people per million, with roughly 900 confirmed cases worldwide, and most cases are tied to activating mutations in the ACVR1 gene.

The study, known as OPTIMA, was a randomized, double-blind, placebo-controlled, multicenter, multinational phase 3 trial in adults with active, genetically confirmed FOP. Registered as NCT05394116, it enrolled 63 adults who were assigned to intravenous treatment every four weeks for 56 weeks: 23 patients received garetosmab at 10 mg/kg, 19 received garetosmab at 3 mg/kg and 21 received placebo. The primary endpoint was the total number of new heterotopic ossification lesions at 56 weeks, measured by whole-body CT scans.

At 56 weeks, the 10 mg/kg group had two new lesions, compared with 19 in the placebo group, a 90% reduction. The 3 mg/kg group had one new lesion, compared with 19 in placebo, a 94% reduction. Regeneron also reported clinician-assessed flare-up results through 56 weeks. The 10 mg/kg arm had nine flare-up events, an 88% reduction versus placebo, while the 3 mg/kg arm had 53 events, a 15% reduction. The placebo group had 66 events. Regeneron said patient-reported flare-ups did not significantly differ between groups.

The findings are notable because garetosmab is designed to neutralize activin A, a signaling protein that abnormally activates the mutated ACVR1, also called ALK2, pathway that drives bone formation in FOP. That makes it a disease-modifying approach aimed at the biology of the condition, rather than simply treating symptoms. In a Regeneron press release, Dr. Kathryn Dahir, the OPTIMA primary investigator, said: “For people living with FOP, every irregular new bone formation is a step toward disability and potential loss of mobility. With the ability to reduce the number of new bone lesions and flare-ups, we now have a new treatment that can positively affect patients.”

At 56 weeks, serious treatment-emergent adverse events were reported in two patients in the 10 mg/kg group, one patient in the 3 mg/kg group and two patients in the placebo group. Common adverse reactions reported in at least 10% of patients included abscesses and other skin conditions, acne, increased hair growth, loss of eyebrow or eyelash hair, oral ulcers, nosebleeds and rash. The phase 3 safety data arrive after earlier scrutiny of garetosmab in the phase 2 LUMINA-1 program, where activity against new bone formation was overshadowed by five deaths in an extension phase, underscoring the need for continued long-term monitoring.

The FDA approved Pasatru, or garetosmab-grts, on Aug. 19, 2026, to reduce the formation of new heterotopic ossification lesions and clinician-assessed flare-ups in adults with FOP. According to Regeneron’s approval materials, the approved dose is 10 mg/kg given intravenously once monthly, with an option to reduce to 3 mg/kg if not tolerated. The approval gives adults with FOP another option alongside Sohonos, or palovarotene, an oral retinoic acid receptor-gamma agonist approved in 2023. Unlike palovarotene, garetosmab is a monthly monoclonal antibody, adding a mechanistically distinct treatment for this ultra-rare disease.