Summary: available economic evidence and the comparator precedent

No cost-effectiveness analysis, budget impact model, or health technology assessment of zilurgisertib has been published. The National Institute for Health and Care Research Innovation Observatory briefing of July 2025 recorded the cost as not yet known and identified no relevant NICE guidance. Mirum states that FOP affects approximately 300 people in the United States and 900 worldwide. No U.S. price has been announced; a Citizens analyst quoted by Reuters estimated an annual cost of about $750,000 and peak worldwide sales of roughly $150 million.

The only economic evaluation in the FOP population located for this report is the 2023 Canadian review of palovarotene. CADTH's reanalysis estimated an incremental cost of $19,020,252 and 1.46 incremental QALYs versus standard of care alone, an ICER of $13,055,900 per QALY gained (Canadian dollars), with drug acquisition representing 99% of total predicted costs; a price reduction of more than 99% would be needed to reach $50,000 per QALY. The committee recommended reimbursement on condition of a price reduction and prescribing by an FOP expert, and CADTH estimated a 3-year public drug plan budget impact of $14,336,341. In England, the NICE highly specialised technologies evaluation of palovarotene was suspended in March 2023 after the negative CHMP opinion and discontinued in January 2025. Sections 4.2.1 through 4.2.7 report the palovarotene budget impact analysis as the closest available precedent; its inputs describe the Canadian population, price, and dosing of palovarotene.

United Kingdom horizon scanning of zilurgisertib

“Estimated Cost The cost of zilurgisertib is not yet known.” (opens the source at this quote in a new tab)
“NICE Guidance No relevant guidance identified.” (opens the source at this quote in a new tab)
“There is currently no treatment option recommended by the National Institute for Health and Care Excellence (NICE) for FOP.” (opens the source at this quote in a new tab)

Analyst sales forecast for zilurgisertib

“Citizens analyst Jonathan Wolleben estimates Atebrioz could cost about $750,000 annually and generate roughly $150 million in peak worldwide sales.” (opens the source at this quote in a new tab)

Canadian reimbursement recommendation for the comparator palovarotene

“CADTH recommends that Sohonos be reimbursed by public drug plans to reduce the formation of heterotopic ossification (HO) in adults and children aged 8 years and above for females and 10 years and above for males with fibrodysplasia ossificans progressiva (FOP), if certain conditions are met.” (opens the source at this quote in a new tab)
“Sohonos should only be reimbursed if prescribed by an expert in the diagnosis and management of FOP and if the cost of Sohonos is reduced.” (opens the source at this quote in a new tab)
“Based on CADTH’s assessment of the health economic evidence, Sohonos does not represent good value to the health care system at the public list price. A price reduction is therefore required.” (opens the source at this quote in a new tab)

Cost-effectiveness of the comparator palovarotene in the Canadian review

“In the sponsor’s base-case analysis, palovarotene plus SoC was associated with an estimated cost of $16,629,383 and 44.03 QALYs over the 80-year horizon, resulting in an ICER of $2,979,324 per QALY gained (incremental costs = $16,471,773; incremental QALYs = 5.53) compared to SoC alone (Table 3).” (opens the source at this quote in a new tab)
“Based on CADTH’s reanalysis, palovarotene plus SoC is more costly (incremental costs = $19,020,252) and more effective (incremental QALYs = 1.46) compared with SoC, resulting in an incremental cost-effectiveness ratio (ICER) of $13,055,900 per QALY gained.” (opens the source at this quote in a new tab)
“The results of CADTH’s reanalyses are driven by palovarotene drug acquisition costs, which represent 99% of the total predicted costs of care.” (opens the source at this quote in a new tab)
“Based on CADTH’s reanalysis, for palovarotene to be considered cost-effective compared to SoC alone at a WTP threshold of $50,000 per QALY, the price of palovarotene would need to be less than $3.24 per mg (e.g., $16.21 per 5 mg tablet), reflecting a price reduction of more than 99%.” (opens the source at this quote in a new tab)

NICE evaluation of the comparator palovarotene

“Please note that following on from information provided to NICE by the company in January 2023, the appraisal was suspended from NICE’s work programme. As no further information has been received from the company the topic has been discontinued” (opens the source at this quote in a new tab)
“The company have advised that the European Medicines Agency Committee for Medicinal Products (CHMP) have issued a negative opinion for Palovarotene to reduce the formation of heterotopic ossification associated with fibrodysplasia ossificans progressiva. Therefore, NICE has decided to suspend this evaluation from its work program until further information is available.” (opens the source at this quote in a new tab)

Budget impact model of zilurgisertib

No evidence found.

Palovarotene budget impact analysis submitted to CADTH: approach and scenarios compared

“The sponsor’s pan-Canadian estimates reflect the aggregated results from provincial budgets (excluding Quebec), as well as the Non-Insured Health Benefits Program.” (opens the source at this quote in a new tab)
“The sponsor compared a reference scenario in which patients received SoC alone to a new drug scenario in which palovarotene was reimbursed as an add-on therapy to SoC, with palovarotene plus SoC assumed to capture 45% of the total market share by year 3, based on the sponsor’s internal estimates and expert opinion.” (opens the source at this quote in a new tab)

Palovarotene budget impact analysis submitted to CADTH: perspective and time horizon

“The BIA was undertaken from the perspective of a Canadian public payer over a 3-year time horizon (Q3 of 2023 through Q2 of 2026) using an epidemiologic approach.” (opens the source at this quote in a new tab)

Zilurgisertib: U.S. and worldwide patient population stated by the manufacturer

“Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, progressive genetic disease affecting approximately 300 people in the United States and 900 worldwide.” (opens the source at this quote in a new tab)

Zilurgisertib: manufacturer estimate of current treatment exposure

“we actually estimate there were more [FOP] patients on clinical studies than on commercial drugs. Which we take as a real statement” (opens the source at this quote in a new tab)

Palovarotene: sales and patient uptake reported by the manufacturer

“Sohonos: flat sales impacted by limited number of new patients in the U.S.” (opens the source at this quote in a new tab)

Sohonos sales, millions of euros	FY 2025	FY 2024
Total	“20.7”	“20.8”
North America	“11.6”	“14.1”

Zilurgisertib: analyst statements on the U.S. patient population and expected treatment preference

“Leerink Partners estimates there are about 300 FOP patients in the U.S. Analyst Joseph Schwartz said in a research note that diagnosis rates for the disorder could rise as new therapies create awareness of the disease and genetic testing increases. He added that clinicians have told Leerink that that they expect patients will prefer Atebrioz’s daily oral formulation versus monthly infusions of Regeneron’s drug.” (opens the source at this quote in a new tab)
“Leerink estimates the drug could achieve $200 million in peak sales, though that figure could change when Mirum releases pricing information.” (opens the source at this quote in a new tab)

United States: age distribution of 284 people with FOP

“Of 284 patients with age data, the average age was 29.3 years; 31 (11%) were 0 to < 10 years, 65 (23%) were ≥ 10 to < 20 years, 63 (22%) were ≥ 20 to < 30 years, 58 (20%) were ≥ 30 to < 40 years, and 67 (24%) were ≥ 40 years.” (opens the source at this quote in a new tab)

Palovarotene budget impact analysis submitted to CADTH: population and uptake inputs

Parameter	Sponsor’s estimate (year 1 / year 2 / year 3)
Prevalence of FOP	“0.000056%”
Proportion of FOP patients aged ≥ 8 years (female) or ≥ 10 years (male)	“88%”
Proportion of patients diagnosed	“90%”
Proportion of diagnosed patients receiving treatment	“100%”
Proportion of patients with public coverage	“Jurisdiction-specific”
Number of patients eligible for drug under review	“10 / 10 / 10”
Uptake of palovarotene plus SoC, new drug scenario	“35% / 40% / 45%”

Palovarotene budget impact analysis: CADTH appraisal of the population inputs

“The sponsor assumed that 90% of patients with FOP would be correctly diagnosed owing to difficulty in correctly diagnosing FOP.” (opens the source at this quote in a new tab)
“For year 1, assuming 35% uptake results in 3 patients anticipated to receive palovarotene plus SoC.” (opens the source at this quote in a new tab)
“In the CADTH base case, CADTH increased the uptake of palovarotene such that 5 patients would receive palovarotene plus SoC in year 1.” (opens the source at this quote in a new tab)

“CADTH’s estimated budget impact of reimbursing palovarotene is based on an estimated prevalence of 0.56 per million, based on Canadian registry data from 2016, resulting in approximately 19 patients with FOP in Canada; however, the Canadian FOP Network estimates that there are 34 patients with FOP in Canada.” (opens the source at this quote in a new tab)

Zilurgisertib: list price not announced as of 28 September 2026

“Mirum, which predicted peak sales of more than $200 million earlier this year for Atebrioz, has not yet revealed a list price and will announce the cost when it becomes available in October, Peetz said.” (opens the source at this quote in a new tab)

Palovarotene budget impact analysis submitted to CADTH: drug and standard-of-care costs

“The sponsor’s analysis included drug acquisition costs for palovarotene based on the sponsor’s submitted price. SoC was assumed by the sponsor to comprise nonsteroidal anti-inflammatory drugs, corticosteroids, and COX-2 inhibitors, and no costs for SoC were included in the model.” (opens the source at this quote in a new tab)
“The annual estimated cost of palovarotene estimated by the sponsor (8 to 14 years: $767,812; 15 to 24 years: $1,163,606; ≥ 25 years: $863,087) was based on the chronic regimen and flare-up regimens and incorporated the estimated annual number of flares per year for each age group based on the MOVE trial.” (opens the source at this quote in a new tab)
“Finally, in the BIA, the sponsor assumed an equal distribution of patients across 3 age groups, in the calculation of the estimated annual per-patient acquisition cost of $869,401 for palovarotene.” (opens the source at this quote in a new tab)

Palovarotene: cost of flare-up dosing

“CADTH estimates that the cost associated with treating a 12-week flare-up ranges from approximately $181,563 to $363,126 per patient, depending on patient age and weight.” (opens the source at this quote in a new tab)
“Costs related to persistent flare-ups or new flare-ups during the course of a flare-up regimen are not captured within the sponsor’s BIA.” (opens the source at this quote in a new tab)

Budget impact model of zilurgisertib: model outcomes

No evidence found.

Palovarotene cost-utility model submitted to CADTH: outcomes estimated

“The analysis was conducted from the perspective of the Canadian public health care payer. Costs and clinical outcomes (life-years [LYs] and quality-adjusted life-years [QALYs]) were estimated over a lifetime time horizon of 80 years (1-year cycle length), discounted at an annual rate of 1.5% per annum.” (opens the source at this quote in a new tab)

Palovarotene budget impact analysis: sponsor and CADTH base cases

“The sponsor estimated that the 3-year budget impact of reimbursing palovarotene to reduce the formation of HO in patients with FOP (females aged 8 years and older; males aged 10 years and older) would be $10,429,302 (year 1: $3,002,028; year 2: $3,472,745; year 3: $3,954,529).” (opens the source at this quote in a new tab)
“In the CADTH base case, the 3-year budget impact is expected to be $14,336,341 (year 1: $4,288,612; year 2: $4,775,024; year 3: $5,272,705) should palovarotene be reimbursed as per the Health Canada indication (i.e., to reduce the formation of HO in adults and children aged 8 years and older for females and 10 years and older for males with FOP).” (opens the source at this quote in a new tab)

Palovarotene budget impact analysis: CADTH scenario analyses

Scenario	Year 1	Year 2	Year 3	Three-year total
CADTH base case	“$4,288,612”	“$4,775,024”	“$5,272,705”	“$14,336,341”
Scenario 1: higher FOP prevalence (1 in 1 million)	“$7,658,235”	“$8,526,829”	“$9,415,545”	“$25,600,609”
Scenario 2: 100% of FOP patients are correctly diagnosed	“$4,765,124”	“$5,305,582”	“$5,858,561”	“$15,929,268”
Scenario 3: 100% public coverage of palovarotene	“$5,823,928”	“$6,484,589”	“$7,160,589”	“$19,469,106”
Scenario 4: 99% price reduction for palovarotene	“$42,886”	“$47,750”	“$52,727”	“$143,363”

Summary: implications of the comparator model for a zilurgisertib budget impact estimate

No budget impact model of zilurgisertib exists, so the Canadian palovarotene analysis is the only modeled precedent for FOP. In that analysis, palovarotene acquisition was the only cost modeled, because no standard-of-care costs were included, and the 3-year budget impact ranged from $143,363 with a 99% price reduction to $25,600,609 with a prevalence of 1 in 1 million, against a CADTH base case of $14,336,341 (Canadian dollars) for an eligible population of about 19 patients. CADTH identified the number of eligible patients, uptake, flare-up dosing, and the omitted standard-of-care costs as the principal uncertainties. Two of these differ for zilurgisertib: its labeled dosage is a fixed 100 mg once daily, supplied as 25 mg tablets in bottles of 120, with no weight-based or flare-up regimen, and the U.S. population stated by the manufacturer is approximately 300 people, of whom only those aged 12 years and older fall within the labeled indication. A plan-level estimate for zilurgisertib requires the launch price, which Mirum plans to announce at the launch expected in October 2026, and the plan's own count of members with FOP.

Palovarotene budget impact analysis: sources of uncertainty identified by CADTH

“The number of patients eligible for palovarotene is uncertain, owing to uncertainty in the prevalence of FOP in Canada, the proportion of patients accurately diagnosed with FOP, and the proportion of patients who would have public coverage for palovarotene.” (opens the source at this quote in a new tab)
“The uptake of palovarotene may be higher than expected by the sponsor.” (opens the source at this quote in a new tab)
“Palovarotene drug acquisition costs are uncertain and may be underestimated.” (opens the source at this quote in a new tab)
“The cost of SoC was not captured in the estimated budget impact and may vary between those receiving palovarotene plus SoC versus SoC alone.” (opens the source at this quote in a new tab)
“The estimated budget impact is highly sensitive to the number of patients eligible for palovarotene and assumptions about its uptake.” (opens the source at this quote in a new tab)

Atebrioz

Economic information and modeling report

Modeling overview