FOSTER CITY, California — October 26, 2026
Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) announced positive results from Cohort 2 of the pivotal PROGRESS study evaluating ATEBRIOZ™ (zilurgisertib) in children aged 6 to under 12 years with fibrodysplasia ossificans progressiva (FOP), an ultra-rare genetic disease characterised by progressive bone formation in muscles and other soft tissues. At Week 24, treatment with zilurgisertib reduced total heterotopic ossification (HO) lesion volume and improved clinician-assessed joint mobility compared with placebo. No patients receiving zilurgisertib developed new HO lesions during the double-blind treatment period. The study enrolled 25 children who were randomly assigned to receive once-daily oral zilurgisertib 75 mg or placebo for 24 weeks, followed by an open-label extension. These findings build on results from Cohort 1, which supported the U.S. Food and Drug Administration’s approval of ATEBRIOZ in September 2026 for adults and children aged 12 years and older with FOP. Mirum plans to submit a supplemental New Drug Application (sNDA) during the first half of 2027 to seek an expanded indication for children aged 6 to under 12 years.
Clinical Results Show Reduced HO Lesion Volume and Improved Mobility
At Week 24, patients receiving zilurgisertib experienced a mean reduction of 8.09 cubic centimetres in total HO lesion volume, compared with a mean increase of 9.14 cubic centimetres among placebo recipients. The reported treatment difference was 14.0 cubic centimetres in favour of zilurgisertib, with a nominal p-value of 0.003. No new HO lesions were reported among the 12 children treated with zilurgisertib, compared with one patient among the 13 children receiving placebo. Improvements were also observed in joint mobility, assessed using the Cumulative Analogue Joint Involvement Scale (CAJIS), a validated measure ranging from 0 to 30, with higher scores indicating greater impairment. Among patients with available assessments, mean CAJIS scores improved by 0.80 points with zilurgisertib, compared with a 0.09-point improvement with placebo. These results are particularly relevant because FOP progressively restricts movement as abnormal bone develops in soft tissues. Although the findings support further evaluation of zilurgisertib in younger children, the results reflect a relatively small cohort and a 24-week controlled treatment period.
Safety Findings Remain Consistent with Earlier PROGRESS Results
Mirum reported that zilurgisertib was generally well tolerated in Cohort 2, with a safety profile consistent with findings from Cohort 1 and no new safety signals identified. All 25 participants completed the 24-week double-blind period and entered the open-label extension, and no patients discontinued treatment during the controlled phase. No growth plate closure was observed in patients receiving zilurgisertib during the study period. Most adverse events were mild or moderate, while serious adverse events and Grade 3 or higher adverse events were infrequent and occurred less often in the zilurgisertib group than in the placebo group. Events reported more frequently among zilurgisertib-treated patients than placebo recipients included arthralgia, cough, fever and vomiting, each affecting three participants, as well as alopecia, nosebleeds, falls, iron deficiency and nasopharyngitis, each reported in two participants. These findings provide additional information on the treatment’s tolerability in younger patients, although continued follow-up will be important to evaluate longer-term safety and effects on growth and development. ATEBRIOZ is contraindicated during pregnancy because animal-study data indicate a risk of fetal harm; patients of reproductive potential should use effective contraception and contact their healthcare provider if pregnancy occurs.
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Planned Regulatory Submission Expands Development for Younger Children
The positive Cohort 2 results support Mirum’s plan to discuss the data with the FDA and submit an sNDA in the first half of 2027, seeking to expand ATEBRIOZ use to children aged 6 to under 12 years. The medicine is an oral activin receptor-like kinase 2 (ALK2) inhibitor designed to target a key biological mechanism underlying FOP. Pathogenic variants in the ACVR1 gene cause abnormal ALK2 activation, leading to heterotopic ossification in muscles, tendons, ligaments and other soft tissues. Mirum’s PROGRESS programme is also evaluating zilurgisertib in Cohort 3, which is enrolling children aged 2 to under 12 years. Full Cohort 2 results are expected to be presented at an upcoming medical meeting. FOP can begin in early childhood and progressively reduce mobility, independence and quality of life, making treatment during younger years an important area of research. The planned regulatory submission remains subject to further discussions and review, and the results in children younger than 12 do not yet establish an expanded approved indication. Mirum licensed zilurgisertib from Incyte for worldwide development and commercialisation and continues to advance its portfolio of medicines for rare and genetic diseases.
Source:Mirum Pharmaceuticals Press release
