The US FDA approved Atebrioz (zilurgisertib), an oral ALK2 inhibitor developed by Incyte (Nasdaq: INCY) and commercialized by Mirum Pharmaceuticals (Nasdaq: MIRM), 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). Atebrioz is administered once daily by mouth, offering an oral treatment option in a rare disease.
The approval was based on data from Cohort 1 of the PROGRESS study, a global, randomized, double-blind, placebo-controlled Phase II trial enrolling 63 patients aged 12 years and older who were randomized 1:1 to zilurgisertib 100 mg once daily or placebo over a 24-week double-blind period followed by an open-label extension. 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, with treatment effects maintained through Week 48 of the open-label extension.
Zilurgisertib selectively inhibits ALK2, the serine/threonine kinase encoded by the ACVR1 gene; in FOP, gain-of-function variants in ACVR1 render ALK2 constitutively active and aberrantly responsive to Activin A, driving pathological bone formation in soft tissues through SMAD1/5/8 phosphorylation.
Another oral ALK2 inhibitor to have run a randomized, placebo-controlled pivotal trial in FOP was fidrisertib, developed by Ipsen. In December 2025, Ipsen reported that the Phase II FALKON trial of fidrisertib did not meet its primary endpoint of reducing new HO versus placebo, and the study was closed.