Zilurgisertib shows early promise in younger children with FOP
A month after US approval for patients aged 12 and over, Mirum Pharmaceuticals has reported that its oral ALK2 inhibitor slowed abnormal bone growth in children aged six to 11 with fibrodysplasia ossificans progressiva.
In brief
Mirum's oral ALK2 inhibitor zilurgisertib cut heterotopic bone volume in 25 children aged 6 to 11 with FOP, a month after US approval from age 12.
- In PROGRESS Cohort 2, 25 children aged six to 11 were randomised to zilurgisertib 75 mg daily or placebo for 24 weeks.
- Total heterotopic ossification volume fell by 8.09 cm³ on the drug and rose by 9.14 cm³ on placebo; the p-value of 0.003 is nominal.
- Mirum plans a supplemental application to the FDA in the first half of 2027.
Mirum Pharmaceuticals has reported that zilurgisertib, its once-daily oral treatment for fibrodysplasia ossificans progressiva (FOP), reduced the volume of abnormal bone in children aged six to 11. The results, from the second cohort of the PROGRESS study, were announced on 26 October 2026.
The data arrive a month after the FDA approved the drug, as Atebrioz, on 25 September 2026 to reduce the volume of new heterotopic ossification in patients aged 12 and older. Mirum licensed zilurgisertib from Incyte for worldwide development and commercialisation.
A disease that starts in childhood
FOP is an ultra-rare genetic disorder affecting roughly 300 people in the US and 900 worldwide, according to Mirum. Pathogenic variants in the ACVR1 gene cause abnormal activation of the ALK2 receptor, which drives bone to form in muscles, tendons and ligaments. Symptoms usually appear in early childhood, and the extra bone accumulates over time, progressively locking joints.
Zilurgisertib is an ALK2 inhibitor, aimed at that underlying mechanism. "Childhood is a critical window in FOP," said Frederick Kaplan of the University of Pennsylvania's Perelman School of Medicine.
What the cohort showed
Cohort 2 randomised 25 children, with a mean age of 8.3 years, to zilurgisertib 75 mg once daily (12 patients) or placebo (13) for 24 weeks. All completed the double-blind period and entered an open-label extension.
At week 24, total heterotopic ossification volume fell by a mean of 8.09 cm³ on zilurgisertib and rose by 9.14 cm³ on placebo. The Hodges-Lehmann treatment difference was 14.0 cm³ in favour of the drug, with a nominal p-value of 0.003. No child on zilurgisertib developed a new lesion, against one on placebo. A clinician-assessed joint mobility score improved by 0.80 points on the drug and 0.09 on placebo, on a 30-point scale, with no p-value reported.
Mirum said the drug was generally well tolerated, with no discontinuations and no growth plate closure among treated children. Arthralgia, cough, fever and vomiting each occurred in three children on zilurgisertib, more often than on placebo.
A cohort of 25, with wide variability and a nominal p-value, is a signal rather than a settled answer.
Reading the numbers
The results come from a company press release, and full data have not yet been presented or peer reviewed. The standard deviations were wide, and the joint mobility analysis covered only 21 children. The approval for older patients rested on Cohort 1, in which 63 patients aged 12 and over showed a 3.2 cm³ fall in new bone volume on zilurgisertib against a 24.6 cm³ rise on placebo, although the prespecified primary endpoint of new lesions did not reach statistical significance.
A crowding field
Zilurgisertib joins palovarotene (Sohonos), approved in the US in 2023 for girls from eight and boys from ten, and garetosmab (Pasatru), approved in August 2026 for adults only. Mirum plans to file a supplemental new drug application for children aged six to under 12 in the first half of 2027. A third cohort, of children aged two to under 12, is enrolling. It will test whether the effect extends to the youngest patients, in whom the disease usually first appears.
