Mirum, Incyte bolster case for approval in rare bone disease despite mid-stage miss

 

While falling short of statistical significance, Incyte and Mirum Pharmaceuticals’ ALK2 inhibitor showed a “clear benefit” in reducing abnormal bone formation in a Phase 2 study of fibrodysplasia ossificans progressiva.

Incyte and Mirum Pharmaceuticals are marching closer toward an approval for their investigational pill in fibrodysplasia ossificans progressiva—even if mid-stage data found no statistical difference in abnormal bone lesions between the drug candidate and placebo.

Sunday, the companies posted data from the Phase 2 PROGRESS study, which compared their oral drug zilurgisertib against placebo in more than 60 patients. At 24 weeks, only one patient in the zilurgisertib arm developed new heterotopic ossification (HO) lesions—abnormal bone formation inside soft tissues. In comparison, five placebo comparators saw such anomalous bone lesions.

The treatment effect, Incyte and Mirum said, was an 81% reduction in favor of zilurgisertib, though this failed to achieve statistical significance, with a p-value of 0.0986.

After the placebo-controlled 24-week observation period, PROGRESS moved into an open-label extension phase, where patients who were initially assigned to placebo were switched to zilurgisertib. After another 24 weeks of follow-up in this portion of the study, PROGRESS found no new abnormal bone lesions in any participant.

“Despite a primary endpoint miss,” Leerink Partners wrote in a Monday note to investors, “these data position ZGB for approval in September . . . with a clear benefit in reducing/preventing new HO lesions.”

Mirum announced last month that the FDA has accepted its drug package for zilurgisertib, with a target action date of September 26.

The analysts added that zilurgisertib “demonstrated improvement across several clinical measurements.” Indeed, aside from reducing abnormal bone formation, Incyte and Mirum on Sunday touted reductions in mean total lesion volume and the average number of new flares for patients on zilurgisertib versus placebo.

Leerink forecasts peak sales of around $200 million for zilurgisertib, which the firm concedes is “modest” for Mirum, which at present is valued at over $6 billion. Incyte is much bigger, with a market cap of more than $20 billion. Still, for Mirum specifically, the firm sees zilurgisertib as providing “greater upside than downside risk” given the biotech’s expertise in executing on rare disease drugs and the high unmet need in this indication.

Fibrodysplasia ossificans progressiva is a rare, genetic disease where bone forms over soft tissues such as muscles, tendons and ligaments. Patients with the condition suffer from severely restricted movement, leading to the complete loss of mobility over time, as well as other complications like difficulty eating, speaking and breathing. Zilurgisertib works by inhibiting the ALK2 receptor, which in patients with fibrodysplasia ossificans progressiva is abnormally active and drives the abnormal bone formation.

https://www.biospace.com/drug-development/mirum-incyte-bolster-case-for-approval-in-rare-bone-disease-despite-mid-stage-miss