Mirum Reports 8.09 cm³ Decline in Heterotopic Ossification Lesions in Children in Atebrioz Study
Key Facts
Mirum Pharmaceuticals announced results from the second cohort of the PROGRESS study, reporting a decline in mean heterotopic ossification lesion volume among children who received zilurgisertib, compared with an increase among those who received placebo after 24 weeks. Mean lesion volume changed by -8.09 cm³ in the treatment group, compared with an increase of 9.14 cm³ in the placebo group. The company estimated the treatment difference at -14.0 cm³ in favor of zilurgisertib, with a nominal p-value of 0.003. The cohort included 25 children aged 6 to under 12 years, a younger group than the current U.S. indication’s age threshold. Mirum plans to submit a supplemental application in the first half of 2027 to expand the indication to include this age group.
Participants were randomly assigned in a 1:1 ratio to receive zilurgisertib at a dose of 75 mg once daily or placebo during a 24-week double-blind treatment period. At the end of this period, none of the 12 children who received treatment had new heterotopic ossification lesions, compared with one child out of 13 in the placebo group. This finding adds another measure to the comparison between the groups, alongside the change in mean lesion volume. CAJIS scores, a measure of physical function in patients with FOP, also improved by a mean of 0.80 points with zilurgisertib, compared with 0.09 points with placebo. Mirum said the full results from the second cohort will be presented at a future medical meeting.
The company said zilurgisertib was generally well tolerated and that its safety profile was consistent with the results from the first cohort, with no new safety signals. No participant discontinued treatment during the double-blind period, according to Mirum. By contrast, the U.S. Food and Drug Administration label warns that ATEBRIOZ may cause fetal harm based on animal data and prohibits its use during pregnancy. Common adverse reactions include headache, joint pain, upper respiratory tract infection, nosebleed and nausea. The safety results reported for this cohort remain limited to the 24-week double-blind follow-up period.
The results come after U.S. approval in September 2026 of ATEBRIOZ to reduce the volume of new heterotopic ossification in adults and children aged 12 years and older with FOP. The approval was based on the first cohort of the PROGRESS study, while the drug’s efficacy and safety had not been established in children under 12, according to the FDA label. In the trial supporting approval, 63 patients were randomly assigned to receive 100 mg daily or placebo for 24 weeks, followed by a 292-week open-label, single-arm extension period. At week 24, mean new heterotopic ossification volume declined by 3.2 cm³ with ATEBRIOZ, compared with an increase of 24.6 cm³ with placebo. The second cohort is testing a 75 mg dose in younger children, making the planned expansion application contingent on evaluating an age group not covered by the current indication.
The FDA describes FOP as a rare genetic condition in which connective tissues, including muscles, tendons and ligaments, progressively turn into bone. The condition can lead to restricted movement, deformities, severe disability and early death, according to the agency. Mirum said enrollment is ongoing in the third PROGRESS cohort, which includes children aged 2 to under 12 years. The company is expected to present the full results from the second cohort at a future medical meeting, without specifying a date for the meeting in its announcement. The next regulatory step it announced is submission of the supplemental application in the first half of 2027 to expand the indication to children aged 6 to under 12 years.