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Product comparison

7 evidence topics · 10 sources

Summary: products approved or in development for fibrodysplasia ossificans progressiva

Three products are approved by the Food and Drug Administration for fibrodysplasia ossificans progressiva, and each acts at a different point in the signaling pathway driven by the gain-of-function ACVR1 (ALK2) variant. Zilurgisertib is an oral ALK2 kinase inhibitor given as 100 mg once daily to patients aged 12 years and older. Palovarotene is an oral retinoic acid receptor gamma agonist given as 5 mg daily with a 12-week 20/10 mg flare-up regimen (weight-based below age 14), labeled for females aged 8 years and older and males aged 10 years and older. Garetosmab-grts is an intravenous activin A antibody given as 10 mg/kg every 4 weeks, labeled for adults only.

The pivotal evidence differs in design and endpoint. Zilurgisertib was compared with placebo in 63 participants for 24 weeks, with total new HO volume (which includes expansion of existing lesions) of −3.2 cm³ versus +24.6 cm³ (Hodges-Lehmann difference −15.8 cm³). Palovarotene was studied in a single-arm trial of 97 participants against an external natural history control of 101 untreated participants, with annualized new HO volume of 9.4 versus 20.3 cm³/year; the trial's prespecified, square-root transformed primary analysis at this interim analysis did not show a statistically significant difference from the control, and the reported reduction rests on post hoc analyses using non-transformed volumes. Garetosmab-grts was compared with placebo in 63 adults for 56 weeks, with 90% and 94% reductions in the number of new HO lesions at 10 mg/kg and 3 mg/kg; its difference in new HO volume was not statistically significant by the prespecified test.

All three labels contraindicate use in pregnancy. Palovarotene carries a boxed warning for embryo-fetal toxicity and premature epiphyseal closure in growing pediatric patients. Garetosmab-grts carries warnings for embryo-fetal toxicity, skin and soft tissue infections, and epistaxis. Zilurgisertib carries one warning, embryo-fetal toxicity. No head-to-head trial was identified, and each label states that adverse reaction rates from one drug's trials "cannot be directly compared to rates in the clinical trials of another drug". Among investigational products, fidrisertib (another ALK2 inhibitor) did not meet its primary endpoint in the 113-participant FALKON trial, and saracatinib and andecaliximab remain in phase 2 and phase 2/3 trials.

Zilurgisertib (Atebrioz): label profile

Attribute	Quoted label text
Mechanism	“Zilurgisertib is an oral, and selective inhibitor of both wild-type ALK2 and pathogenic ALK2 (R206H mutation).”
Indication and age	“ATEBRIOZ is indicated to reduce the volume of total new heterotopic ossification (HO) in adults and pediatric patients aged 12 years and older with fibrodysplasia ossificans progressiva (FOP).”
Dosage	“The recommended dosage of ATEBRIOZ is 100 mg orally once daily with or without food”
Dosage form	“ATEBRIOZ Tablets: 25 mg of zilurgisertib, film-coated”
Pivotal trial	“Sixty-three patients (28 adults and 35 pediatric patients aged 12 years of age and older) with FOP were randomized 1:1 to treatment with ATEBRIOZ 100 mg or placebo once daily for 24 weeks”
Efficacy endpoint	“Total new HO lesion volume includes expansion of baseline HO lesion burden as well as any new discrete HO”
Efficacy result	“At Week 24, the mean change (SD) from baseline in total new HO volume was −3.2 cm³ (19.9) in the zilurgisertib group and +24.6 cm³ (51.9) in the placebo group, resulting in a Hodges-Lehmann treatment difference of −15.8 cm³ (95% CI: -32.1, -6.0).”
Contraindication	“ATEBRIOZ is contraindicated in pregnancy.”
Warnings and precautions	“Embryo-Fetal Toxicity: Can cause fetal harm.”
Most common adverse reactions	“Most common adverse reactions (≥ 10%): headache, arthralgia, upper respiratory tract infection, epistaxis, and nausea.”
Pediatric patients	“The safety and effectiveness of ATEBRIOZ have not been established in pediatric patients younger than 12 years of age.”

Palovarotene (Sohonos): label profile

Attribute	Quoted label text
Mechanism	“Through binding to RARγ, palovarotene decreases the BMP/ALK2 downstream signaling pathway by inhibiting the phosphorylation of SMAD1/5/8, which reduces ALK2/SMAD-dependent chondrogenesis and osteocyte differentiation resulting in reduced endochondral bone formation.”
Indication and age	“SOHONOS is indicated for the reduction in volume of new heterotopic ossification in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP).”
Daily dosage	“The recommended SOHONOS daily dosage for adults and pediatric patients 14 years and older is 5 mg daily.”
Flare-up dosage	“The recommended SOHONOS flare-up dosage for adults and pediatric patients 14 years and older is 20 mg daily for 4 weeks, followed by 10 mg daily for 8 weeks (for a total of 12 weeks of flare-up treatment), even if symptoms resolve earlier, then return to daily dosing of 5 mg.”
Pivotal trial	“Study PVO-1A-301 (NCT03312634, Study 301) was a single arm study in 97 subjects with FOP with R206H mutation aged 4 years and older utilizing the Natural History Study (NHS, PVO-1A-001) as an external control (n=101).”
Efficacy endpoint	“The primary efficacy endpoint was annualized volume of new heterotopic ossification (HO) as assessed by low-dose, whole body CT (WBCT) imaging (excluding head).”
Efficacy result	“The mean annualized new HO was 9.4 cm3/year in subjects receiving the chronic/flare-up SOHONOS treatment and 20.3 cm3/year in untreated subjects in the NHS based on a linear mixed effect model.”
Boxed warning	“Premature epiphyseal closure occurs in growing pediatric patients treated with SOHONOS, close monitoring is recommended”
Contraindications	“SOHONOS is contraindicated in pregnancy.”

Garetosmab-grts (Pasatru): label profile

Attribute	Quoted label text
Mechanism	“Garetosmab-grts is a human IgG4 monoclonal antibody that specifically binds to and inhibits signaling by activin A to block the activation of FOP-mutant ACVR1 and reduce the formation and progression of new heterotopic bone lesions.”
Indication and age	“PASATRU is indicated to reduce formation of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva (FOP).”
Dosage	“The recommended starting dosage of PASATRU is 10 mg/kg administered as an intravenous infusion over 60 minutes once every 4 weeks.”
Pivotal trial	“The efficacy of PASATRU was evaluated in Study 1 (NCT05394116), a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial in 63 adults with FOP confirmed by an ACVR1 FOP-causing mutation.”
Efficacy endpoint	“The primary efficacy endpoint was the number of new HO lesions at Week 56 assessed by low-dose, whole-body computed tomography (WBCT) imaging”
Efficacy result, new lesions	“Statistically significant reductions in the number of new HO lesions at Week 56 were observed in patients receiving PASATRU 10 mg/kg every 4 weeks or 3 mg/kg every 4 weeks compared to placebo (90% reduction or 94% reduction for PASATRU 10 mg/kg or 3 mg/kg, respectively, compared to placebo).”
Efficacy result, flare-ups	“The rate ratio (95% CI) compared to placebo was 0.12 (0.03, 0.42) for PASATRU 10 mg/kg, and 0.85 (0.26, 2.73) for PASATRU 3 mg/kg.”
Efficacy result, new HO volume	“These findings were not statistically significant based on the pre-specified Wilcoxon rank-sum test.”
Contraindication	“PASATRU is contraindicated during pregnancy.”
Warnings and precautions	“Skin and Soft Tissue Infections: Have occurred in patients treated with PASATRU.”
Pediatric patients	“The safety and effectiveness of PASATRU have not been established in pediatric patients.”

Fidrisertib: phase 2 trial did not meet its primary endpoint

“PARIS, FRANCE, 19 December 2025 – Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the pivotal Phase II FALKON trial did not meet its primary endpoint of reducing new heterotopic ossification (HO) in adults and children living with fibrodysplasia ossificans progressiva (FOP) vs. placebo, as a result the study will be closed.” (opens the source at this quote in a new tab)
“Fidrisertib is an oral, highly selective and potent small molecule inhibitor of pathogenic variants of the ALK2 kinase, the underlying root cause of FOP.” (opens the source at this quote in a new tab)
“Part A is a global, multi-center, placebo-controlled, parallel-group, 3-arm trial, in which 113 patients aged 5 years of age or older with the R206H ACVR1 mutation or other FOP variants associated with progressive HO, were enrolled and randomized to receive either high dose-weight based or low dose weight-based fidrisertib or placebo. The primary endpoint is annualized change from baseline in HO volume.” (opens the source at this quote in a new tab)

Saracatinib: phase 2a trial design

“The STOPFOP team identified AZD0530 (saracatinib) as a potent inhibitor of the ALK2/ ACVR1 -kinase which is the causative gene for this rare bone disease.” (opens the source at this quote in a new tab)
“The STOPFOP trial is a phase 2a study. It is designed as a European, multicentre, 6-month double blind randomized controlled trial of AZD0530 versus placebo, followed by a 12-month trial comparing open-label extended AZD0530 treatment with natural history data as a control. Enrollment will include 20 FOP patients, aged 18–65 years, with the classic FOP mutation (ALK2 R206H).” (opens the source at this quote in a new tab)

Andecaliximab: phase 2/3 trial in pediatric and adult participants

“This study is researching an experimental drug called andecaliximab. The study will include pediatric and adult patients with fibrodysplasia ossificans progressiva (FOP).” (opens the source at this quote in a new tab)

“Reduces Activin-A release from macrophages and matrix stores; likely multimodal actions on all HO factors” (opens the source at this quote in a new tab)