Mirum Pharmaceuticals, Inc. filed a Form 8-K on October 26, 2026, announcing positive results from Cohort 2 of its pivotal PROGRESS study evaluating ATEBRIOZ (zilurgisertib) in pediatric patients aged 6 to less than 12 years with fibrodysplasia ossificans progressiva.

Key Highlights

  • Cohort 2 enrollment: 25 pediatric patients aged 6 to less than 12 years were randomized 1:1 to once-daily oral zilurgisertib 75 mg (n=12) or placebo (n=13) in a 24-week double-blind period.
  • HO lesion volume: At Week 24, mean total heterotopic ossification lesion volume decreased by 8.09 cm3 in the zilurgisertib group versus an increase of 9.14 cm3 in the placebo group, a treatment difference of -14.0 cm3 (nominal p=0.003).
  • No new lesions: Zero zilurgisertib-treated patients developed new HO lesions, compared with 1 of 13 (7.7%) placebo patients.
  • Joint mobility (CAJIS): Mean CAJIS scores improved by 0.80 points with zilurgisertib versus 0.09 points with placebo at Week 24.
  • Safety profile: No patients discontinued treatment during the double-blind period, no growth plate closure was observed in zilurgisertib-treated patients, and no new safety signals were identified.
  • sNDA planned: The company disclosed plans to submit a supplemental New Drug Application in the first half of 2027 to expand the ATEBRIOZ indication to patients aged 6 to less than 12 years.
  • Existing approval: ATEBRIOZ was approved by the U.S. FDA in September 2026 for adult and pediatric patients aged 12 years and older with FOP, based on PROGRESS Cohort 1 data.

PROGRESS Cohort 2: Zilurgisertib Results in Younger Pediatric FOP Patients

According to the filing, Cohort 2 of the PROGRESS study enrolled 25 pediatric patients with a mean age of 8.3 years at baseline and a mean of 5.0 years since initial diagnosis. All patients completed the 24-week double-blind period and entered the open-label extension. Mirum Pharmaceuticals, listed on NASDAQ:MIRM, reported that the primary efficacy findings showed zilurgisertib 75 mg once daily reduced mean total HO lesion volume by 8.09 cm3 (standard deviation 15.58), while the placebo group experienced a mean increase of 9.14 cm3 (standard deviation 11.66), yielding a Hodges-Lehmann estimate of treatment difference of -14.0 cm3 and a nominal p-value of 0.003 by Wilcoxon rank-sum test.

Joint mobility, assessed using the Cumulative Analogue Joint Involvement Scale (CAJIS) - a validated measure scored from 0 (no impairment) to 30 (maximum impairment) - improved by a mean of 0.80 points in zilurgisertib-treated patients compared with 0.09 points in the placebo group. The filing noted that in untreated patients with FOP, CAJIS scores are reported to worsen by approximately 0.5 points per year. These assessments were based on n=10 (zilurgisertib) and n=11 (placebo) patients.

The filing described the safety profile as "generally well tolerated" and "consistent with that observed in PROGRESS Cohort 1." Adverse events occurring in more than 10% of zilurgisertib-treated patients and at a higher frequency than placebo included arthralgia, cough, pyrexia, and vomiting (3 subjects each), and alopecia, epistaxis, fall, iron deficiency, and nasopharyngitis (2 subjects each). Serious adverse events and Grade 3 or higher adverse events were described as occurring less frequently in the zilurgisertib group than in the placebo group. The company also disclosed that Cohort 3, evaluating zilurgisertib in patients aged 2 to less than 12 years, is currently enrolling. The filing contains forward-looking statements, which the company cautioned are subject to risks and uncertainties described in its other regulatory filings.

What Was Disclosed

Mirum Pharmaceuticals filed an 8-K on October 26, 2026, reporting Cohort 2 results from the PROGRESS study of ATEBRIOZ in pediatric FOP patients aged 6 to less than 12 years, including efficacy and safety data, and announcing plans for a 2027 sNDA submission.