Atebrioz (zilurgisertib)

The FDA approved zilurgisertib on September 25, 2026, as the third treatment for FOP, to reduce the volume of total new HO in patients aged 12 years and older. The approval rests on one phase 2 trial cohort of 63 participants with a 24-week placebo-controlled period. The protocol-specified primary endpoint, the proportion of participants with new HO lesions, did not reach statistical significance, and efficacy was established on total new HO volume, a measure that includes expansion of existing lesions. Data after Week 24 come from an open-label extension in which all participants received zilurgisertib, reported as interim results through Week 48. The effect of these radiographic changes on joint function, mobility, and survival has not been reported, and a published analysis of palovarotene states that there is no consensus threshold for a clinically meaningful reduction in new HO volume.

No head-to-head trial has compared zilurgisertib with palovarotene or garetosmab-grts, and the pivotal trials differ in design and endpoint: palovarotene was studied in a single-arm trial of 97 participants against an external natural history control, and garetosmab-grts in a 56-week placebo-controlled trial of 63 adults with the number of new HO lesions as the primary endpoint. The zilurgisertib label includes pediatric patients aged 12 years and older, a group in which the garetosmab-grts label states that safety and effectiveness have not been established, and safety and effectiveness of zilurgisertib have not been established in patients younger than 12 years. Over 24 weeks, the most common adverse reactions (10% or more) were headache, arthralgia, upper respiratory tract infection, epistaxis, and nausea, and the label warning is embryo-fetal toxicity; the label states that the clinical relevance of hepatic iron accumulation and preneoplastic findings in rats, including the potential carcinogenic risk in humans, is uncertain. No U.S. price or budget impact model for zilurgisertib is available.