FDA Approves Regeneron’s Pasatru for Rare Bone-Formation Disorder

Rare Daily Staff

The U.S. Food and Drug Administration has approved Regeneron Pharmaceuticals’ Pasatru for adults with fibrodysplasia ossificans progressiva, an ultra-rare genetic disease in which bone forms abnormally in muscles and other connective tissues.

The company said Pasatru is the first FDA-approved treatment shown in a placebo-controlled trial to reduce both new abnormal bone lesions and clinician-assessed disease flare-ups in adults with the condition.

Fibrodysplasia ossificans progressiva, or FOP, causes a process known as heterotopic ossification, in which bone develops outside the normal skeleton. The abnormal bone can form in muscles, tendons and ligaments, gradually restricting movement and making everyday activities—including eating, speaking, walking and breathing—more difficult.

Pasatru is a fully human monoclonal antibody designed to block Activin A, a protein implicated in abnormal bone formation in people with FOP. It is administered by intravenous infusion every four weeks, generally beginning at milligrams per kilogram of body weight. The dose may be reduced to milligrams per kilogram if the higher dose is not tolerated.

The FDA approval was based on the OPTIMA trial, which enrolled adults with active FOP. Participants received one of two Pasatru doses or placebo for weeks.

At the higher dose, patients developed two new abnormal bone lesions, compared with among those receiving placebo—a percent reduction, according to Regeneron. Patients receiving the lower dose developed one new lesion, representing a percent reduction versus placebo.

The higher-dose group also had nine clinician-assessed flare-ups during the study, compared with in the placebo group, an percent reduction. The lower-dose group had flare-ups, a percent reduction. Patient-reported flare-ups did not differ significantly between the treatment and placebo groups.

“Every irregular new bone formation is a step toward disability and potential loss of mobility,” said Kathryn Dahir of Vanderbilt University, a primary investigator in the trial. She said the treatment could offer a new way to alter the course of the disease.

Pasatru carries important safety warnings. It should not be used during pregnancy because it can cause serious birth defects, according to the company. People who can become pregnant should have a pregnancy test before starting treatment and use effective contraception during treatment and for six months after their final dose.

The treatment can also cause skin and soft-tissue infections, including abscesses and cellulitis, as well as nosebleeds that may occasionally require medical care. Common side effects reported in the trial included abscesses, acne, increased hair growth, eyebrow loss, mouth sores, nosebleeds, inflammation around the nails and rash.

Regeneron said a separate trial, OPTIMA , in adolescents and children with FOP is expected to begin later this year. The medicine is also under regulatory review in the European Union, with additional submissions planned internationally.