Joanne Quan, MD, Chief Medical Officer of Mirum Pharmaceuticals, discusses results from the PROGRESS study of zilurgisertib in patients with fibrodysplasia ossificans progressiva (FOP).
FOP is a disorder in which skeletal muscle and connective tissue are gradually ossified. This condition leads to bone formation outside the skeleton that restricts movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and moving down the body and into the limbs. People with FOP are born with abnormal big toes which can be helpful in making the diagnosis. Trauma, such as a fall or invasive medical procedure, or a viral illness may trigger episodes of muscle swelling and inflammation. These flareups last for several days to months and often result in permanent bone growth in the injured area. FOP is almost always caused by a genetic change at the same place in the ACVR1 gene.
Phase 2 results from Cohort 1 of the PROGRESS study (NCT05090891) evaluating zilurgisertib in adolescents and adults with FOP were presented at the ENDO 2026 annual meeting. Zilurgisertib is an investigational oral activin receptor-like kinase 2 (ALK2) inhibitor.
Of 63 patients randomized to receive zilurgisertib (n=32) or placebo (n=31), 61 had week 48 whole-body CT scan data available at the time of the open-label extension analysis. The primary endpoint was the proportion of patients with new heterotopic ossification (HO) lesions on whole-body CT scan at week 24.
At week 24, fewer patients receiving zilurgisertib developed new HO lesions compared with placebo (3.1% vs 16.7%), representing an 81% reduction versus placebo.Total new lesion volume was reduced by 99.6% with zilurgisertib versus placebo, and total lesion volume was reduced with zilurgisertib while increasing with placebo. The mean annualized total number of new flares was also lower for zilurgisertib.
In the open-label period, no new lesions were reported regardless of treatment assignment. From week 24-48, mean decreases in total volume of all HO lesions were observed in both zilurgisertib-randomized and crossover patients. The mean number of annualized new flares was low for both patient groups.
The most common adverse events in the zilurgisertib group were FOP flare-up or aching/pain due to FOP, headache, upper respiratory tract infection, arthralgia, epistaxis, and nausea, with a similar profile in the extension. Most adverse events were mild or moderate and none led to dose reduction or discontinuation with zilurgisertib across both periods.
Zilurgisetib for FOP has a PDUFA date of September 26, 2026.
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To learn more about FOP and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/