Mirum Pharmaceuticals and Incyte Announce Positive Pivotal Phase 2 Results from PROGRESS Study of Zilurgisertib in Fibrodysplasia Ossificans Progressiva | Business

Mirum Pharmaceuticals and Incyte Announce Positive Pivotal Phase 2 Results from PROGRESS Study of Zilurgisertib in Fibrodysplasia Ossificans Progressiva | Business

June 14, 2026 discoverhiddenusacom Health

Mirum Pharmaceuticals and Incyte reported Phase 2 results for zilurgisertib, an oral ALK2 inhibitor for fibrodysplasia ossificans progressiva (FOP), showing an 81% reduction in patients developing new heterotopic ossification (HO) lesions compared to a placebo group at Week 24. According to data presented at the ENDO 2026 annual meeting, the drug also led to a 99.9% reduction in the total volume of new HO lesions during the same period.

The PROGRESS study evaluated 63 adolescents and adults aged 12 and older with a mean age of about 21. Researchers randomized 32 patients to receive 100 mg of zilurgisertib once daily and 31 patients to receive a placebo.

How does zilurgisertib affect FOP lesions?

The drug reduced the development of new HO lesions, which occur when bone forms in soft tissues. In the placebo group, five patients developed new lesions, compared to only one patient in the zilurgisertib group, according to the companies.

Total existing HO lesion volume decreased in patients receiving the drug, while the placebo group saw an increase (p-value=0.004). Annualized flare activity was also lower for those on zilurgisertib, averaging 2.34 compared to 4.55 in the placebo group.

During an open-label extension through Week 48, no new HO lesions were observed. This included both patients who stayed on the drug and those who crossed over from the placebo group to active treatment.

Did You Know? FOP is an ultra-rare genetic disease that affects approximately 300 patients in the U.S. and 900 patients worldwide, with diagnoses typically occurring in early childhood.

What was the safety profile of the drug?

Zilurgisertib was generally well-tolerated over the 24-week placebo-controlled period. According to the study data, most adverse events were mild or moderate, and no patients discontinued treatment or required dose reductions due to these events.

What was the safety profile of the drug?

The most common adverse events for patients receiving the drug included FOP flare-ups or aching/pain (25%), headache (21.9%), and upper respiratory tract infections (21.9%). Other reported events included arthralgia (18.8%), epistaxis (12.5%), and nausea (12.5%).

Expert Insight: Samantha Carter notes that the 99.9% reduction in new lesion volume represents a significant clinical signal for a disease where soft tissue ossification is typically irreversible. The fact that no patients discontinued treatment suggests a manageable safety profile that could support long-term administration.

When will the FDA make a decision?

The U.S. Food and Drug Administration has accepted the New Drug Application (NDA) for zilurgisertib for patients 12 years and older. The agency granted the application Priority Review status, according to Mirum Pharmaceuticals.

The Prescription Drug User Fee Act (PDUFA) target action date is September 26, 2026. If approved, the companies may move forward with commercialization to support the FOP community.

Frequently Asked Questions

What is zilurgisertib?
It is an investigational, oral, small molecule ALK2 inhibitor designed to block the ALK2 receptor, which is abnormally active in most FOP patients and leads to bone formation in soft tissues.

Who participated in the PROGRESS study?
Cohort 1 of the study included 63 adolescents and adults aged 12 and older with FOP.

What happened to placebo patients after 24 weeks?
Patients who crossed over from the placebo to zilurgisertib saw a decrease in total HO lesion volume and no new HO lesions were observed between Week 24 and Week 48.

How could a potential treatment for ultra-rare diseases change the way these conditions are managed in the U.S.?

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