FDA Approves Mirum and Incyte’s FOP Drug Atebrioz

Rare Daily Staff

The U.S. Food and Drug Administration has approved Atebrioz, a once-daily oral treatment from Mirum Pharmaceuticals and Incyte for adults and adolescents ages 12 and older with fibrodysplasia ossificans progressiva, or FOP, an ultra-rare genetic disease.

The drug is approved to reduce the volume of total new heterotopic ossification, the abnormal formation of bone in muscles, tendons, ligaments and other soft tissues that can progressively restrict movement in people with FOP.

FOP is caused by pathogenic variants in the ACVR1 gene, which lead to abnormal activation of the ALK2 pathway and trigger bone formation outside the skeleton. Symptoms typically begin in childhood, and accumulating lesions can cause severe disability and loss of independence over time.

“Today marks an important milestone for people living with FOP, bringing a new treatment option to adult and pediatric patients living with this devastating disease,” said Chris Peetz, CEO of Mirum.

Atebrioz is an ALK2 inhibitor designed to target a central disease mechanism in FOP and reduce the formation of new abnormal bone. Incyte developed the drug and licensed it to Mirum for worldwide development and commercialization.

The approval was based on Cohort 1 of the global phase 2 PROGRESS trial, which enrolled 63 patients with FOP ages 12 and older. Participants were randomly assigned to receive Atebrioz 100 mg once daily or placebo for 24 weeks, followed by an open-label extension.

The trial’s measure of total new heterotopic ossification lesion volume included both the expansion of lesions present at the beginning of the study and newly developed discrete lesions during the placebo-controlled period.

The most commonly reported adverse reactions during the 24-week placebo-controlled portion of the study were headache, joint pain, upper respiratory tract infection, nosebleeds and nausea. Most adverse events were mild or moderate, and the companies said no adverse event led to treatment discontinuation or dose reduction during that period.

Atebrioz’s prescribing information warns that the drug can cause fetal harm based on animal studies. Patients of reproductive potential should use effective contraception. Patients who become pregnant should stop treatment and contact their health care provider, the companies said.

The FDA also awarded Incyte a Rare Pediatric Disease Priority Review Voucher, which can be used to seek priority review for a future drug application that would not otherwise qualify. The vouchers are potentially lucrative because they are transferable. Most recently, they have sold for more than $200 million each.

Mirum and Incyte are continuing the pediatric PROGRESS program in younger children with FOP. Enrollment has been completed in Cohort 2, involving children ages 6 to younger than 12, while enrollment is ongoing in Cohort 3, involving children ages 2 to younger than 12.

A marketing authorization application for Atebrioz is also under review by the European Medicines Agency, supported by data from the cohort of patients ages 12 and older.

Michelle Davis, executive director of the International Fibrodysplasia Ossificans Progressiva Association, said an additional treatment option could give patients, families and clinicians more flexibility in managing a disease whose effects vary substantially among individuals. “For families living with FOP, having additional treatment options means having greater flexibility in managing a complex, lifelong disease,” Davis said.

Photo: Chris Peetz, CEO of Mirum.