Mirum Pharmaceuticals and Incyte have announced that the US Food and Drug Administration (FDA) has approved Atebrioz (zilurgisertib) tablets to reduce the volume of total new Heterotopic Ossification (HO) in adult and pediatric patients aged 12 years and older with Fibrodysplasia Ossificans Progressiva (FOP). The recommended dose of Atebrioz is 100 mg administered orally, once daily.

Chris Peetz, Chief Executive Officer, Mirum, said, “Today marks an important milestone for people living with FOP, bringing a new treatment option to adult and pediatric patients living with this devastating disease. At Mirum, we are driven to serve rare disease communities where the unmet need is significant and the opportunity to make a difference is profound. The approval of Atebrioz reflects what can be achieved when industry, researchers and patient communities work together, and we remain committed to fostering that spirit of collaboration in FOP.”

Atebrioz was developed by Incyte and licensed to Mirum Pharmaceuticals for worldwide development and commercialisation.

Atebrioz is a once-daily oral Activin receptor-Like Kinase 2 (ALK2) inhibitor designed to target the disease-driving pathway at the center of FOP biology. In people living with FOP, pathogenic variants in the ACVR1 gene result in the abnormal activation of ALK2, leading to the formation of bone in muscles, tendons, ligaments and other soft tissues through a process known as HO. As HO lesions develop and accumulate over time, they can progressively restrict movement and lead to significant disability.

Michelle Davis, Executive Director, International Fibrodysplasia Ossificans Progressiva Association (IFOPA), said, “For families living with FOP, having additional treatment options means having greater flexibility in managing a complex, lifelong disease. Every person’s experience with FOP is different, and expanding treatment options gives patients, families and their physicians the opportunity to consider what may be right for their individual needs.”

Atebrioz was approved based on data from Cohort 1 of the PROGRESS study evaluating zilurgisertib in adult and pediatric patients aged 12 years and older with FOP. Efficacy was established based on total new HO lesion volume. Total new HO lesion volume includes expansion of baseline HO lesion burden as well as any new discrete HO that developed during the 24-week double-blind period. At week 24, mean total new HO lesion volume decreased by 3.2 cm³ in patients receiving zilurgisertib compared with an increase of 24.6 cm³ in placebo-treated patients. Treatment effects were maintained through week 48 of the open-label extension.

Robert Pignolo, MD, PhD, Robert and Arlene Kogod, Professor, Geriatric Medicine, Mayo Clinic College of Medicine and lead investigator for the PROGRESS study, said, “FOP is a lifelong disease in which the accumulation of HO leads to increasing disability and loss of function. Having another treatment option is meaningful in a progressive disease like FOP, particularly for adolescents who may be earlier in the course of their disease.”

Zilurgisertib was generally well tolerated during the 24-week placebo-controlled period of the study. The most common adverse reactions were headache, arthralgia, upper Respiratory Tract Infection (RTI), epistaxis and nausea. Most Adverse Events (AEs) were mild or moderate in severity, and no AEs led to treatment discontinuation or dose reduction.

Atebrioz will be available through Mirum Access Plus (MAP), a patient support program designed to help patients, families and healthcare providers navigate treatment access. MAP provides insurance coverage and access support, financial assistance for eligible patients, personalised patient support and educational resources for patients and caregivers.

Atebrioz is expected to be commercially available in the US in October, with eligible patients paying as little as $0 per month through MAP.

With this approval, the FDA also issued a Rare Pediatric Disease Priority Review Voucher (PRV) to Incyte. The voucher can be used for a subsequent drug application that would not otherwise qualify for a Priority Review (PR).

In the European Union (EU), a Marketing Authorisation Application (MAA) for zilurgisertib is currently under review by the European Medicines Agency (EMA), supported by data from Cohort 1 (patients aged 12 years and older) of the PROGRESS study.

The PROGRESS development program also continues to advance, with enrollment completed in Cohort 2 of children aged 6 to <12 years, and enrollment underway in Cohort 3 of children aged 2 to <12 years.