FDA approves Mirum and Incyte’s Atebrioz (zilurgisertib), an oral ALK2 inhibitor for FOP, reducing total new heterotopic ossification volume in Phase 2 PROGRESS data.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Atebrioz (zilurgisertib), an oral activin receptor-like kinase 2 (ALK2) inhibitor from Mirum Pharmaceuticals and Incyte, to reduce the volume of total new heterotopic ossification (HO) in adults and pediatric patients aged 12 years and older with fibrodysplasia ossificans progressiva (FOP). The recommended dose is 100 mg once daily.
The approval makes Atebrioz the third FDA-approved therapy for FOP, following palovarotene (Sohonos), approved in 2023, and garetosmab-grts (Pasatru), approved in August 2026.
FDA Approval Based on Reduction in New HO Volume
The decision was supported by Cohort 1 of the Phase 2 PROGRESS study, a randomized, double-blind, placebo-controlled trial involving 63 patients aged 12 years and older. Participants received zilurgisertib 100 mg once daily or placebo for 24 weeks, followed by an open-label extension.
The FDA based efficacy on the change from baseline in total new HO volume, assessed using whole-body CT scans. At Week 24, patients receiving zilurgisertib had a mean 3.2 cm³ decrease in total new HO volume, compared with a 24.6 cm³ increase in the placebo group.
Total new HO volume incorporated both the expansion of existing HO lesions and newly developed discrete lesions during the placebo-controlled period.
Statistical Findings Show Different Effects Across HO Measures
The PROGRESS results require an important distinction between the study’s lesion-based and volume-based outcomes.
At Week 24, 1 of 32 patients (3.1%) receiving zilurgisertib developed a new HO lesion compared with 5 of 31 patients (16.7%) receiving placebo. This represented an 81% relative reduction, but the difference did not reach statistical significance (P=0.0986).
In contrast, the volume of newly formed HO lesions was reduced by 99.9% with zilurgisertib compared with placebo, with a nominal P value of less than 0.0001. Total existing HO lesion volume also decreased with zilurgisertib while increasing with placebo, with a nominal P value of 0.004.
This distinction is clinically relevant because the FDA’s approval rests on the reduction in total new HO volume, rather than the statistically nonsignificant difference in the proportion of patients who developed new lesions.
ALK2 Inhibition Targets the FOP Disease Pathway
FOP is caused by pathogenic variants in ACVR1, which encodes the ALK2 receptor. Abnormal activation of this pathway promotes heterotopic bone formation in muscles, tendons, ligaments and other soft tissues.
Zilurgisertib inhibits ALK2, targeting a central signaling pathway involved in the abnormal bone formation that progressively restricts movement and physical function in people with FOP.
Safety Profile and Dosing
Atebrioz is administered orally at 100 mg once daily, with or without food. The most common adverse reactions reported during the placebo-controlled period were headache, joint pain, upper respiratory tract infection, nosebleeds and nausea.
The prescribing information warns that Atebrioz can cause fetal harm based on animal studies. Patients of reproductive potential should use effective contraception and discontinue treatment and contact their healthcare provider if pregnancy occurs.
Mirum Leads Commercialization After Incyte Licensing Deal
The approval follows an April 2026 agreement under which Mirum licensed exclusive worldwide rights to develop and commercialize zilurgisertib from Incyte. Under the agreement, Incyte received an upfront payment and remains eligible for development and regulatory milestones, sales-based milestones and tiered royalties on worldwide net sales.
The FDA also issued a Rare Pediatric Disease Priority Review Voucher to Incyte following the approval. The voucher can be used for a subsequent drug application that otherwise would not qualify for priority review.
Atebrioz is expected to become commercially available in the United States in October through Mirum Access Plus, which provides insurance access support and financial assistance for eligible patients.
Pediatric Development and Global Regulatory Review
The development program is continuing in younger children. PROGRESS Cohort 2 has completed enrollment in patients aged 6 to under 12 years, while Cohort 3 is evaluating children aged 2 to under 12 years.
In Europe, the marketing authorization application for zilurgisertib remains under review by the European Medicines Agency.
With Atebrioz, the FOP treatment landscape now includes three FDA-approved therapies, while ongoing studies are expanding evaluation of ALK2 inhibition into younger patients. The approval also establishes total new HO volume as the regulatory efficacy measure supporting zilurgisertib’s use in patients aged 12 years and older.
Reference
Mirum Pharmaceuticals and Incyte Announce U.S. FDA Approval of Atebrioz™ (zilurgisertib) for Adult and Pediatric Patients with Fibrodysplasia Ossificans Progressiva, Mirium Pharmaceuticals, 25 September 2026
Mirum Pharmaceuticals and Incyte Announce U.S. FDA Approval of Atebrioz™ (zilurgisertib) for Adult and Pediatric Patients with Fibrodysplasia Ossificans Progressiva, Incyte, 25 September 2026
To Assess the Efficacy, Safety, and Tolerability of INCB000928 in Participants with Fibrodysplasia Ossificans Progressiva (Progress), ClinicalTrials.gov ID NCT05090891
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.