Positive PROGRESS results for zilurgisertib in children aged 6–11 with FOP – Mirum

Mirum Pharmaceuticals, Inc. announced positive results from Cohort 2 of the pivotal PROGRESS study of ATEBRIOZ (zilurgisertib), an oral activin receptor-like kinase 2 (ALK2) inhibitor, in pediatric patients aged 6 to <12 years with fibrodysplasia ossificans progressiva (FOP).

At Week 24, zilurgisertib reduced total heterotopic ossification (HO) lesion volume and improved clinician-assessed joint mobility. No zilurgisertib-treated patients developed new HO lesions.

The results build on data from PROGRESS Cohort 1, which supported the FDA approval of ATEBRIOZ in September 2026 for adult and pediatric patients aged 12 years and older with FOP. Mirum plans a supplemental New Drug Application (sNDA) submission in H1 2027 to expand the indication to pediatric patients aged 6 to <12 years.

“These results represent an important advance for younger children living with FOP,” said Rob Myers, M.D., Chief Medical Officer of Mirum. “The reduction in total HO volume and absence of new lesions seen with zilurgisertib build on the positive results previously observed in adolescents and adults in Cohort 1 of PROGRESS. We look forward to discussing these findings with the FDA to expand access to ATEBRIOZ for younger children living with this debilitating disease.”

“FOP is a devastating genetic disease that leads to progressive loss of mobility, independence, quality of life, and shortened lifespan,” said Frederick S. Kaplan, M.D., Isaac and Rose Nassau Professor of Orthopaedic Molecular Medicine at the University of Pennsylvania Perelman School of Medicine. “Childhood is a critical window in FOP, so a therapy targeting the underlying cause of the disease is especially important for this young age group. Results such as these offer hope that we may be able to slow disease progression in children before its most serious consequences arise.”

PROGRESS Cohort 2 Results

Cohort 2 of the PROGRESS study enrolled 25 pediatric patients aged 6 to <12 years with FOP. Patients were randomized 1:1 to receive once-daily oral zilurgisertib 75 mg (n=12) or placebo (n=13) during a 24-week double-blind period, followed by an open-label extension. The mean age at baseline was 8.3 years, with a mean of 5.0 years since initial diagnosis. All patients completed the double-blind period and entered the open-label extension.

At Week 24, mean total HO lesion volume decreased by 8.09 cm³ in patients receiving zilurgisertib, compared with an increase of 9.14 cm³ in patients receiving placebo (nominal p=0.003). No zilurgisertib-treated patients developed new HO lesions.

Improvements in clinician-assessed joint mobility were also observed. Joint mobility was assessed using the Cumulative Analogue Joint Involvement Scale (CAJIS), a validated measure of physical function in FOP scored from 0 (no impairment) to 30 (maximum impairment). At Week 24, CAJIS scores improved by a mean of 0.80 points in patients receiving zilurgisertib, compared with 0.09 points in patients receiving placebo. In untreated patients with FOP, CAJIS scores are reported to worsen by approximately 0.5 points per year.

Zilurgisertib was generally well tolerated, with a safety profile consistent with that observed in PROGRESS Cohort 1. No new safety signals were identified. No patients discontinued treatment during the double-blind period, and no zilurgisertib-treated patients experienced growth plate closure. Additional safety findings included:

i) Most adverse events were mild or moderate in severity.

ii) Serious adverse events and Grade ≥3 adverse events were infrequent and occurred less frequently in patients receiving zilurgisertib than in those receiving placebo.

iii) Adverse events occurring in more than 10% of zilurgisertib-treated patients and at a higher frequency than with placebo included arthralgia, cough, pyrexia, and vomiting (3 subjects each), and alopecia, epistaxis, fall, iron deficiency, and nasopharyngitis (2 subjects each).

ATEBRIOZ is approved by the FDA to reduce the volume of total new HO in adult and pediatric patients aged 12 years and older with FOP. Total new HO lesion volume includes expansion of baseline HO lesion burden as well as any new discrete HO that developed during the 24-week double-blind period.

Full Cohort 2 results will be presented at an upcoming medical meeting. Cohort 3 of the PROGRESS study, which is evaluating zilurgisertib in pediatric patients aged 2 to <12 years, is currently enrolling.

About the PROGRESS Study

PROGRESS is a global, randomized, double-blind, placebo-controlled Phase 2 study evaluating the efficacy and safety of zilurgisertib in patients with fibrodysplasia ossificans progressiva (FOP). PROGRESS Cohort 1 enrolled 63 patients 12 years of age and older who were randomized 1:1 to receive zilurgisertib 100 mg once daily or placebo during a 24-week double-blind treatment period, followed by an open-label extension. Results from Cohort 1 have been reported through Week 48. The PROGRESS study is also evaluating the safety and efficacy of zilurgisertib in younger patients with FOP. Cohort 2 enrolled 25 patients aged 6 to <12 years who were randomized 1:1 to receive zilurgisertib 75 mg once daily or placebo during a 24-week double-blind treatment period, followed by an open-label extension. Cohort 3, which is evaluating zilurgisertib in patients aged 2 to <12 years, is currently enrolling.