Mirum Pharmaceuticals has reported positive data from cohort 2 of the pivotal Phase II PROGRESS trial assessing Atebrioz (zilurgisertib) in paediatric patients aged six to under 12 years with fibrodysplasia ossificans progressiva (FOP).
Over 24 weeks, the oral activin receptor-like kinase 2 (ALK2) inhibitor reduced total heterotopic ossification (HO) lesion volume and improved clinician-assessed joint mobility, with treated patients developing no new lesions.
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Building on the trial outcome, Mirum plans to submit a supplemental new drug application (NDA) to the US Food and Drug Administration (FDA) in the first half of 2027 to expand the therapy’s indication to this age group.
The 24-week double-blind study evaluated 25 children with a mean baseline age of 8.3 years and a mean of 5.0 years from diagnosis.
Participants received either once-daily oral zilurgisertib 75mg (n=12) or placebo (n=13) before entering an open-label extension.
At week 24, mean total HO lesion volume fell by 8.09cm³ with zilurgisertib versus an increase of 9.14cm³ with placebo.
On the 0 to 30 Cumulative Analogue Joint Involvement Scale (CAJIS), scores improved by a mean of 0.80 points in the zilurgisertib group against 0.09 points on placebo. Untreated patients typically experience an annual worsening of 0.5 points.
Mirum Pharmaceuticals chief medical officer Rob Myers said: “These results represent an important advance for younger children living with FOP.
“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.”
No participants discontinued therapy during the double-blind phase, and no zilurgisertib recipients experienced growth plate closure.
Serious and Grade 3 or higher adverse events were infrequent and occurred less often than with placebo, with most events rated mild or moderate.
Events occurring in over 10% of treated patients and exceeding placebo rates included cough, arthralgia, pyrexia, and vomiting in three subjects each, alongside epistaxis, alopecia, fall, nasopharyngitis, and iron deficiency in two subjects each.
FOP is a genetic disorder where activin A receptor type 1 (ACVR1) variants drive ALK2 activation, causing bone formation in soft tissues including ligaments, muscles, and tendons.
The FDA cleared Atebrioz in September 2026 for patients aged 12 and older following cohort 1.
In March 2026, Mirum Pharmaceuticals completed enrolment in the Phase III EXPAND study assessing Livmarli (maralixibat) for patients aged six months and above with cholestatic pruritus linked to rare cholestatic liver diseases, including biliary atresia.
