Atebrioz (zilurgisertib)

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, autosomal dominant disorder caused by gain-of-function variants in ACVR1 (ALK2); an estimated 97% of affected individuals carry the R206H variant. It is characterized by congenital malformations of the great toes and by progressive heterotopic ossification (HO) in specific anatomic patterns, often after episodic flare-ups. The estimated minimum prevalence is 0.88 per million in the United States (2020), and estimates in France are 1.36 per million (2012) and 1.39 per million (2020); the manufacturer states that the disease affects approximately 300 people in the United States and 900 worldwide. In an international survey, 87% of individuals initially received an incorrect diagnosis, and the mean time from symptom onset to correct diagnosis was 4.1 years.

Disability is cumulative: most patients are “confined to a wheelchair by the third decade of life” and require lifelong assistance with activities of daily living. Among 60 deaths reported in the international FOP community, the median age at death was 40 years; the estimated median lifespan was 56 years (95% CI 51 to 60), and cardiorespiratory failure from thoracic insufficiency syndrome accounted for 54% of deaths. In an international burden-of-illness survey, the mean EQ-5D-5L index score of participants aged 13 years and older was 0.24 (n = 152), and it decreased from 0.61 at the lowest level of mobility restriction to 0.05 at the highest.

In a French case-control study, mean total annual healthcare expenditure in individuals with FOP was more than 10 times that of matched controls from a societal perspective and 14 times from a payer perspective. In the international survey, U.S. respondents in the two highest levels of mobility restriction reported mean FOP-related costs of approximately 22,000 U.S. dollars, with an upper range of approximately 164,000 U.S. dollars at the highest level; family members spent a mean of 8 hours per day providing care, and 51.3% of primary caregivers reported adapting their careers.