FDA Approves Zilurgisertib for Fibrodysplasia Ossificans Progressiva

The FDA has approved zilurgisertib (Atebrioz, Mirum Pharmaceuticals) tablets to reduce the volume of total new heterotopic ossification (HO) in adults and pediatric patients aged 12 years and older with fibrodysplasia ossificans progressiva (FOP). The agency called it the third treatment approved for FOP. The recommended starting dosage is 100mg orally once daily, with or without food.

The FDA describes FOP as a rare genetic disease caused by a mutation in activin A receptor type 1 (ACVR1). Over time, muscle, tendons, and ligaments turn into bone, which leads to limited movement, deformities, severe disability, and early death. Zilurgisertib is an oral activin receptor-like kinase 2 (ALK2) inhibitor. According to Mirum and Incyte, pathogenic ACVR1 variants abnormally activate ALK2, and that activation drives HO. Incyte developed the drug and licensed it to Mirum for worldwide development and commercialization.

The approval was based on Cohort 1 of the phase 2 PROGRESS trial (NCT05090891). In that cohort, 63 patients were randomized 1:1 to zilurgisertib 100mg or placebo once daily for 24 weeks, followed by an open-label extension. The efficacy endpoint was the change from baseline in total new HO volume on whole-body CT. This measure counts both growth of existing lesions and new discrete lesions. At week 24, mean total new HO volume fell by 3.2 cm³ with zilurgisertib and rose by 24.6 cm³ with placebo. The companies said the treatment effects held through week 48 of the extension.

Based on animal data, zilurgisertib can cause fetal harm. The FDA said patients of reproductive potential should use effective contraception and should stop the drug if they become pregnant. The most common adverse reactions were headache, arthralgia, upper respiratory tract infection, epistaxis, and nausea. The FDA also noted that certain drugs listed in the label should not be taken with zilurgisertib. The companies reported that most adverse events during the placebo-controlled period were mild or moderate, and none led to treatment discontinuation or dose reduction.

The drug received Fast Track, Priority Review, and orphan drug designation, and Incyte received a rare pediatric disease priority review voucher. A marketing authorization application is under review by the European Medicines Agency. Enrollment has been completed in a pediatric PROGRESS cohort of children aged 6 to younger than 12 years, and enrollment is underway in a separate cohort of children aged 2 to younger than 12 years. 

Sources: US Food and Drug Administration. FDA approves third treatment for fibrodysplasia ossificans progressiva. News release. US Food and Drug Administration; September 25, 2026. Accessed September 28, 2026.

Mirum Pharmaceuticals, Incyte. Mirum Pharmaceuticals and Incyte announce US FDA approval of Atebrioz (zilurgisertib) for adult and pediatric patients with fibrodysplasia ossificans progressiva. Press release. Incyte; September 25, 2026. Accessed September 28, 2026.