Incyte and Mirum Pharmaceuticals announced on June 16 that they are moving closer to approval for their investigational pill, zilurgisertib, in fibrodysplasia ossificans progressiva, despite mid-stage clinical data not meeting the primary statistical endpoint.
The companies released results from the Phase 2 PROGRESS study, which compared oral zilurgisertib with placebo in more than 60 patients. After 24 weeks, one patient receiving zilurgisertib developed new heterotopic ossification lesions—abnormal bone growth in soft tissues—while five patients in the placebo group experienced such lesions. Incyte and Mirum said this represented an 81% reduction in favor of zilurgisertib. However, the difference did not reach statistical significance, with a p-value of 0.0986.
Following the initial observation period, all participants entered an open-label extension phase where those initially on placebo switched to zilurgisertib. Over another 24 weeks of follow-up during this phase, no new abnormal bone lesions were reported among any participants.
Leerink Partners commented on Monday that, "despite a primary endpoint miss," these results "position ZGB for approval in September . . . with a clear benefit in reducing/preventing new HO lesions." The analysts also stated that zilurgisertib "demonstrated improvement across several clinical measurements." In addition to reducing abnormal bone formation, Incyte and Mirum highlighted reductions in mean total lesion volume and average number of new flares among patients taking the drug compared to those on placebo.
Mirum previously announced that the U.S. Food and Drug Administration has accepted its application for zilurgisertib with a target action date set for September 26. Leerink forecasts peak sales around $200 million for the drug but described this as “modest” given Mirum’s current valuation at over $6 billion and Incyte’s market capitalization exceeding $20 billion. The firm added that for Mirum specifically, there is “greater upside than downside risk” due to its expertise with rare disease drugs and high unmet need among patients.
Fibrodysplasia ossificans progressiva is a rare genetic disorder characterized by bone forming over soft tissues such as muscles or tendons. This leads to severely restricted movement over time along with complications including difficulty eating, speaking, or breathing. Zilurgisertib acts by inhibiting ALK2 receptor activity believed responsible for driving abnormal bone formation in affected individuals.
