Name: Atebrioz (zilurgisertib) in Fibrodysplasia ossificans progressiva: Pharmacodynamics
Published: 2026-09-27T12:28:00-04:00

Exposure-response relationship

“The exposure-response relationship and time course of the pharmacodynamic response for the effectiveness and safety of zilurgisertib have not been fully characterized.” (opens the prescribing information at this quote)

Cardiac electrophysiology

“Clinically significant QT interval prolongation was not observed at concentrations up to 6.7 times the mean maximum concentrations achieved with the recommended daily dose of ATEBRIOZ.” (opens the prescribing information at this quote)

“As both studies indicated a dose‐dependent effect of zilurgisertib on heart rate, individualized QT correction (QTcI) was used as the primary endpoint for QTc analysis.” (opens the source at this quote in a new tab)
“No significant relationship between zilurgisertib plasma concentration and change in QTcI was identified; zilurgisertib did not have a clinically relevant effect on QTc prolongation. QT effect >10 ms could therefore be excluded within the dose range studied (up to 300 mg BID). No clinically meaningful effects on cardiac conduction (PR and QRS intervals) or any categorical PR or QRS outliers were observed.” (opens the source at this quote in a new tab)

Suppression of heterotopic ossification in a mouse model

“Zilurgisertib fully suppresses HO in a pediatric mouse model of injury-induced FOP and therefore holds great potential as a novel targeted disease-modifying therapy for FOP.” (opens the source at this quote in a new tab)
“Compound 15 (zilurgisertib) was tested at four doses administered orally bid for 6 weeks in a pediatric FOP model of injury-induced HO following postnatal induction of expression of the ALK2[R206H] human FOP mutation (Alk2(R206H); Rosa26-CreERT2 compound heterozygous mice).” (opens the source at this quote in a new tab)
“Radiographic imaging revealed dose-dependent potent suppression of heterotopic bone formation and corresponding preservation of joint mobility after the 6 week treatment period.” (opens the source at this quote in a new tab)
“The lowest tested dose of 2 mg/kg bid potently reduced HO formation and fully maintained joint mobility. Complete prevention of ankylosing heterotopic bone formation was observed at bid doses ≥5 mg/kg.” (opens the source at this quote in a new tab)

Threshold pharmacokinetic/pharmacodynamic relationship for heterotopic ossification suppression

“This consistently strong efficacy observed across all dose levels suggests an atypical pharmacokinetic/pharmacodynamic (PK/PD) relationship, in which the drug merely needs to achieve a threshold level of target engagement to trigger a durable, disease-modifying effect on heterotopic bone formation.” (opens the source at this quote in a new tab)

Hepcidin and iron effects in preclinical models

“Zilurgisertib was shown to inhibit hepcidin production in cellular assays and to improve hemoglobin levels in 2 mouse models of hepcidin-associated anemia” (opens the source at this quote in a new tab)

“The liver findings in rats are consistent with the pharmacologic effects of zilurgisertib on iron homeostasis secondary to ALK2 inhibition.” (opens the prescribing information at this quote)

Iron parameters in participants with FOP

“Compared to placebo, ATEBRIOZ-treated patients experienced mean increases in serum iron, hemoglobin, and transferrin saturation levels; the mean values for all three measures remained within the normal range.” (opens the prescribing information at this quote)