Summary

No cost-effectiveness analysis, budget impact model, or health technology assessment of lirafugratinib was identified, and no price had been announced as of September 2026. Elevar Therapeutics expects United States availability by the fourth quarter of 2026. Under the December 2024 license, Relay Therapeutics is eligible for up to $75 million in upfront and regulatory milestones, up to $425 million in commercial milestones, and tiered royalties up to the low-teens percentage; by June 30, 2026 Relay had received $5.0 million on execution, $3.7 million on transfer of materials, and $10.0 million in milestone payments, and remained eligible for up to $485.0 million.

Comparator economics come from pemigatinib and futibatinib. Canada's Drug Agency recommended reimbursement of pemigatinib in 2025 on condition of a price reduction, after a 2022 recommendation not to reimburse; its reanalysis estimated incremental cost-effectiveness ratios of $252,718 and $261,226 per quality-adjusted life-year versus active symptom control alone and mFOLFOX plus active symptom control, and price reductions exceeding 95% would be needed to reach $50,000 per quality-adjusted life-year. From a Taiwanese payer perspective, pemigatinib was not cost-effective over 5 years at a hypothesized price (NT$5,814,700 per quality-adjusted life-year versus mFOLFOX), whereas a lifetime analysis using final FIGHT-202 data estimated US$83,475 per quality-adjusted life-year, below the threshold applied. A Greek analysis estimated €69,928 per quality-adjusted life-year versus mFOLFOX plus active symptom control, and a United States conference poster comparing pemigatinib with gemcitabine and cisplatin reported an overall survival-based incremental cost-effectiveness ratio of $183,628. NICE recommended pemigatinib in July 2021 (TA722) as a life-extending treatment at the end of life, on condition of a commercial arrangement; the company's base-case incremental cost-effectiveness ratios, including an updated patient access scheme, were £42,076 and £45,029 per quality-adjusted life-year gained compared with mFOLFOX plus active symptom control and active symptom control alone, the committee-preferred assumptions gave between £45,051 and £45,808 and between £44,354 and £45,010, against an upper limit of £50,000 per quality-adjusted life-year gained for a life-extending treatment at the end of life. NICE recommended futibatinib (TA1005) as an alternative to pemigatinib, which it concluded was the only relevant comparator: matching-adjusted indirect comparison hazard ratios for futibatinib compared with pemigatinib were 0.95 (95% CI 0.72 to 1.21) for overall survival and 1.07 (95% CI 0.86 to 1.30) for progression-free survival, a cost comparison found similar costs, and all incremental cost-effectiveness ratios are confidential because of the confidential pemigatinib discount. A second Taiwanese analysis of a biomarker-driven regimen (pemigatinib for FGFR2 fusion-positive and mFOLFOX for fusion-negative intrahepatic cholangiocarcinoma) against fluorouracil estimated NT$3,411,098 per quality-adjusted life-year, with a probability of cost-effectiveness of 53.2%, and a positive incremental net monetary benefit when the price of pemigatinib was reduced by 40%. No Institute for Clinical and Economic Review assessment was identified. A systematic review of 20 economic studies in biliary tract cancer concluded that most current-price targeted agents were not cost-effective in the jurisdictions studied. Worldwide net revenue of pemigatinib across all indications was $86.7 million in 2025.

Economic model, cost-effectiveness analysis, or health technology assessment of lirafugratinib

No evidence found.

Announced price of lirafugratinib

No evidence found.

Announced United States launch timing for lirafugratinib

“Lyrfigtu is expected to be available to patients in the U.S. by Q4 2026.” (opens the source at this quote in a new tab)
“FDA approval does not guarantee commercial success or any particular level of market adoption, reimbursement, revenue generation, or clinical outcomes in broader patient populations.” (opens the source at this quote in a new tab)

Partnership economics for lirafugratinib: Elevar Therapeutics license terms

“Relay Therapeutics has potential to receive up to $500 million in upfront, regulatory and commercial milestone payments, including $75 million in upfront and regulatory milestones, plus up to double digit royalties on global sales” (opens the source at this quote in a new tab)
“Elevar will assume full responsibility for all further development activities, including submission of the NDAs, all subsequent clinical development, and global commercialization for FGFR2-driven CCA and FGFR2-altered other solid tumors.” (opens the source at this quote in a new tab)
“Relay Therapeutics is eligible to receive up to $75 million in upfront and regulatory milestones, plus up to $425 million in potential commercial milestone payments, as well as tiered royalties up to the low-teens percentage.” (opens the source at this quote in a new tab)

Partnership economics for lirafugratinib: payments received and milestones outstanding

“In December 2024, we and Elevar Therapeutics, Inc., or Elevar, entered into an exclusive global licensing agreement, or the Elevar Agreement, pursuant to which Elevar was granted global development and commercialization rights for lirafugratinib.” (opens the source at this quote in a new tab)
“Under the terms of the Elevar Agreement, we received $5.0 million upon execution, $3.7 million upon transfer of active pharmaceutical ingredient and other materials, and $10.0 million in milestone payments as of June 30, 2026.” (opens the source at this quote in a new tab)
“We are eligible to receive up to $485.0 million in regulatory and commercial milestone payments, as well as tiered royalties.” (opens the source at this quote in a new tab)
“During the six months ended June 30, 2026 the Company recognized $3.4 million of revenue from the Elevar Agreement, specifically upon receipt of certain milestone payments, as well as upon transfer of active pharmaceutical ingredient and other materials.” (opens the source at this quote in a new tab)

“During the year ended December 31, 2025, we recognized $15.4 million of license and other revenue from the Elevar Agreement, specifically in connection with the completion of each of our performance obligations thereunder in 2025, as well as receipt of certain milestone payments.” (opens the source at this quote in a new tab)
“In connection therewith, certain milestone payments and royalties were excluded from the transaction price as of December 31, 2025, because such payments were variable consideration fully constrained.” (opens the source at this quote in a new tab)

Systematic review of published economic evidence in biliary tract cancer

“Twenty studies were included: 13 cost-effectiveness or cost–utility analyses and seven cost-of-illness or resource-use studies.” (opens the source at this quote in a new tab)
“First-line immunotherapy combinations and biomarker-directed targeted therapies frequently produced ICERs above jurisdiction-specific willingness-to-pay thresholds at current prices, often requiring substantial price reductions to approach cost-effectiveness.” (opens the source at this quote in a new tab)
“Real-world studies showed high resource use and costs, particularly with hospitalizations and later treatment lines.” (opens the source at this quote in a new tab)
“A central finding is that most current-price immunotherapies and targeted agents were not cost-effective in the jurisdictions studied.” (opens the source at this quote in a new tab)

Economic evidence specific to the second-line setting in biliary tract cancer

“The second-line economic literature was relatively sparse and concentrated on biomarker-selected therapies rather than on cytotoxic chemotherapy.” (opens the source at this quote in a new tab)
“we did not identify a dedicated peer-reviewed cost-effectiveness analysis of FOLFOX versus active symptom control in BTC” (opens the source at this quote in a new tab)
“Overall, the second-line evidence supports a cautious interpretation: targeted agents may offer clinically relevant options for molecularly selected patients, but at current prices, they have generally not been shown to be cost-effective in the jurisdictions studied.” (opens the source at this quote in a new tab)

Cost-effectiveness analyses of pemigatinib in previously treated intrahepatic cholangiocarcinoma

“Pemigatinib was not cost-effective at the hypothesized price of NT $17,820/13.5 mg.” (opens the source at this quote in a new tab)
“The ICER versus mFOLFOX and 5-FU was NT $3,411,098/QALY” (opens the source at this quote in a new tab)
“ICER vs. mFOLFOX: NT $6,268,528/QALY; vs. 5-FU/LV: NT $5,670,555/QALY” (opens the source at this quote in a new tab)

Net product revenue of pemigatinib, all indications worldwide

“The following table presents our disaggregated revenues for the periods presented (in thousands):” (opens the source at this quote in a new tab)

Year	PEMAZYRE revenues, net (USD thousands)
2025	“86,727”
2024	“81,748”
2023	“83,642”

Health technology assessment of pemigatinib in Canada: 2025 reimbursement recommendation

“Canada’s Drug Agency (CDA-AMC) recommends that Pemazyre be reimbursed by public drug plans for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 fusion or other rearrangement if certain conditions are met.” (opens the source at this quote in a new tab)
“Pemazyre should only be reimbursed if prescribed by clinicians with expertise in managing patients with gastrointestinal malignancies and if the cost of Pemazyre is reduced.” (opens the source at this quote in a new tab)
“Based on the CDA-AMC assessment of the health economic evidence, Pemazyre 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)
“The cost-effectiveness of pemigatinib is highly uncertain due to the high degree of uncertainty of the magnitude of clinical benefit of pemigatinib compared with ASC alone and mFOLFOX plus ASC.” (opens the source at this quote in a new tab)
“In 2022, pemigatinib was reviewed by CDA-AMC for the treatment of adult patients with previously treated, unresectable, locally advanced, or metastatic CCA with an FGFR2 fusion or other rearrangement and received a do not reimburse recommendation.” (opens the source at this quote in a new tab)

Health technology assessment of pemigatinib in Canada: 2022 reimbursement recommendation

“The pCODR Expert Review Committee (pERC) recommends that pemigatinib not be reimbursed for the treatment of adults with previously treated, unresectable locally advanced, or metastatic cholangiocarcinoma (CCA) with a FGFR2 fusion or other rearrangement.” (opens the source at this quote in a new tab)

Health technology assessment of pemigatinib in England, as reported by the manufacturer

“In July 2021, the U.K.’s National Institute for Health and Care Excellence (“NICE”) recommended PEMAZYRE for patients with cholangiocarcinoma with an FGFR2 fusion or rearrangement that have progressed after at least one prior line of systemic therapy.” (opens the source at this quote in a new tab)
“NICE’s guidance enables all eligible patients in England and Wales to have access to PEMAZYRE through the National Health Service.” (opens the source at this quote in a new tab)

Health technology assessment of pemigatinib in England: NICE TA722 recommendation

“Pemigatinib is recommended, within its marketing authorisation, as an option for treating locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that has progressed after systemic therapy in adults. It is recommended only if the company provides pemigatinib according to the commercial arrangement.” (opens the source at this quote in a new tab)
“Current treatment for advanced cholangiocarcinoma with an FGFR2 fusion or rearrangement that has progressed after systemic therapy is symptom control, with or without modified folinic acid, 5-fluorouracil and oxaliplatin (mFOLFOX) chemotherapy.” (opens the source at this quote in a new tab)
“Clinical evidence from 1 study suggests that pemigatinib may be more effective than current treatments. This is uncertain because the study did not directly compare pemigatinib with symptom control or mFOLFOX.” (opens the source at this quote in a new tab)
“Pemigatinib meets NICE's criteria for a life-extending treatment at the end of life. The cost-effectiveness estimates are uncertain but are likely to be within the range that NICE considers a cost-effective use of NHS resources. So, pemigatinib is recommended.” (opens the source at this quote in a new tab)

Health technology assessment of pemigatinib in England: comparators and committee-preferred ICERs

“The clinical experts advised that the relevant comparators currently used in routine clinical practice include mFOLFOX+ASC and ASC alone. The committee concluded that these are the most appropriate comparators for this appraisal.” (opens the source at this quote in a new tab)
“It concluded that the matching adjusted indirect comparison suggests pemigatinib was more effective than the comparators, but that this was uncertain.” (opens the source at this quote in a new tab)
“For the short life-expectancy criterion, the company's base-case model estimated a mean undiscounted life expectancy of 8.0 months for mFOLFOX+ASC and 7.3 months for ASC alone. For the life-extension criterion, the company's base-case model estimated an undiscounted mean incremental life expectancy with pemigatinib of 25.6 months compared with mFOLFOX+ASC and 26.4 months compared with ASC alone.” (opens the source at this quote in a new tab)
“For a life-extending treatment at the end of life, the upper limit of the range usually considered to represent a cost-effective use of NHS resources is £50,000 per quality-adjusted life year (QALY) gained. The committee noted that the company's new base-case ICERs for pemigatinib, including an updated patient access scheme, were £42,076 per QALY gained compared with mFOLFOX+ASC, and £45,029 per QALY gained compared with ASC alone.” (opens the source at this quote in a new tab)
“Using these preferred assumptions, the ICER was between £45,051 and £45,808 per QALY gained compared with mFOLFOX+ASC, and between £44,354 and £45,010 per QALY gained compared with ASC alone.” (opens the source at this quote in a new tab)
“Other scenarios, including using the generalised gamma curve to extrapolate long-term survival with pemigatinib, resulted in higher ICERs.” (opens the source at this quote in a new tab)
“It concluded that the cost-effectiveness estimates for pemigatinib suggest it is an acceptable use of NHS resources for a life-extending treatment at the end of life. So pemigatinib was recommended for routine use in the NHS.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of pemigatinib from the Taiwanese payer perspective, 2020 FIGHT-202 data

“Pemigatinib was not cost-effective compared to mFOLFOX or 5-FU in the base-case analysis.” (opens the source at this quote in a new tab)
“According to the NCCN guidelines, the daily use of pemigatinib 13.5 mg at the hypothesized NHIA price of NT$17,820/13.5 mg was not cost-effective compared to mFOLFOX or 5-FU.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of pemigatinib from the Taiwanese payer perspective, 2024 FIGHT-202 final data

“In 2023, Taiwan’s National Health Insurance Administration granted provisional payment for pemigatinib for patients with advanced ICC and FGFR2 fusions/rearrangements.” (opens the source at this quote in a new tab)
“Pemigatinib is cost-effective with updated long-term benefits from the pivotal trial in the lifetime simulation for advanced patients with advanced ICC and FGFR2 fusions/rearrangements.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of a biomarker-driven pemigatinib or mFOLFOX regimen versus fluorouracil from the Taiwanese payer perspective

“Although the new second-line genetic-based and biomarker-driven regimen of pemigatinib/mFOLFOX appears not cost effective for patients with advanced intrahepatic cholangiocarcinoma in the base-case analysis, our analysis suggests it is highly likely to be cost effective in the case of a 40% price reduction on pemigatinib.” (opens the source at this quote in a new tab)
“In Taiwan, only pemigatinib has been approved by the Taiwan FDA for the aforementioned indications but has not been reimbursed by the Taiwan National Health Insurance (NHI) as of November 2022.” (opens the source at this quote in a new tab)
“Currently, mFOLFOX is not reimbursed for patients with ICC in Taiwan; consequently, pemigatinib is compared to the far lower priced chemotherapy 5-FU, making pemigatinib even more unfavorable.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of pemigatinib from a Greek payer perspective

“Pemigatinib, a therapy covering the unmet medical need of patients with previously treated locally advanced or metastatic CCA with an FGFR2 fusion or rearrangement, was estimated to be cost-effective compared with mFOLFOX+ASC and ASC alone in Greece.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of pemigatinib from a United States perspective

“Pemigatinib has a higher cost but is also more effective than gemcitabine/cisplatin.” (opens the source at this quote in a new tab)
“The higher cost of pemigatinib is attributed to the direct cost, while the bulk of gemcitabine/cisplatin therapy’s cost is from the treatment of adverse events.” (opens the source at this quote in a new tab)

Health technology assessment of futibatinib in England: NICE TA1005 recommendation

“Futibatinib is recommended, within its marketing authorisation, as an option for treating locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that has progressed after at least 1 line of systemic treatment in adults. Futibatinib is only recommended if the company provides it according to the commercial arrangement.” (opens the source at this quote in a new tab)
“Usual treatment for locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement that has progressed after systemic treatment is pemigatinib. Futibatinib would be an alternative option to pemigatinib.” (opens the source at this quote in a new tab)
“There are no clinical trials directly comparing futibatinib with pemigatinib. An indirect comparison of futibatinib and pemigatinib suggests that they may have similar effectiveness, but this is uncertain.” (opens the source at this quote in a new tab)
“A cost comparison suggests that futibatinib has similar costs to pemigatinib. So, futibatinib is recommended.” (opens the source at this quote in a new tab)

Health technology assessment of futibatinib in England: comparator, indirect comparison, and cost comparison

“The EAG suggested that mFOLFOX should also be considered as a comparator because it may still be used in this population.” (opens the source at this quote in a new tab)
“But it noted that the company had positioned futibatinib as an alternative to pemigatinib, rather than after pemigatinib, so it could not evaluate futibatinib in this positioning. The committee considered the clinical expert's view that all people with a known FGFR2 alteration would have pemigatinib. It concluded that pemigatinib was the only relevant comparator.” (opens the source at this quote in a new tab)
“MAIC (adjusted) hazard ratios for futibatinib compared with pemigatinib were 0.95 (95% CI 0.72 to 1.21) for overall survival and 1.07 (95% CI 0.86 to 1.30) for progression-free survival.” (opens the source at this quote in a new tab)
“The committee concluded that there was no clear evidence of a difference in efficacy between pemigatinib and futibatinib.” (opens the source at this quote in a new tab)
“The company's resulting QALY weight of 1.2 was validated by the EAG. The committee concluded that the severity weight of 1.2 applied to the QALYs was appropriate.” (opens the source at this quote in a new tab)
“Because pemigatinib has a confidential discount, all ICERs are confidential and cannot be reported here.” (opens the source at this quote in a new tab)
“The committee concluded that the cost for futibatinib was similar to that of pemigatinib. It agreed that the cost-effectiveness estimates for futibatinib were within the range that NICE considers an acceptable use of NHS resources. So, the committee recommended futibatinib as an alternative option to pemigatinib for previously treated locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement.” (opens the source at this quote in a new tab)

Institute for Clinical and Economic Review assessment of FGFR inhibitors in cholangiocarcinoma

No evidence found.

Health technology assessment of zanidatamab, a second-line targeted therapy for advanced biliary tract cancer, in England

“There is enough evidence to show that zanidatamab provides benefits and value for money, so it can be used routinely across the NHS in this population.” (opens the source at this quote in a new tab)
“If further treatment is suitable, people usually have FOLFOX chemotherapy with active symptom control (ASC). If this is not suitable, people usually have ASC only.” (opens the source at this quote in a new tab)

“The committee concluded that FOLFOX plus ASC, or ASC alone, were the relevant comparators for zanidatamab.” (opens the source at this quote in a new tab)
“The committee concluded that an acceptable ICER would be towards the upper end of the range NICE considers a cost-effective use of NHS resources (£25,000 to £35,000 per QALY gained).” (opens the source at this quote in a new tab)
“The committee was satisfied that its preferred assumptions produced an ICER that was within the range that NICE considers to be a cost-effective use of NHS resources.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of ivosidenib in previously treated IDH1 mutant cholangiocarcinoma from an Italian perspective

“The main reported outcomes are reported in Table 1. Ivosidenib obtained 7962 € per month OS-gained. FOLFOX obtained 7676 € per month OS-gained.” (opens the source at this quote in a new tab)
“Furthermore, let us consider that this price is based on ex-factory costs and that the real, confidential, is based on further discounts (indicative reduction of a further 40%) [15]. It means that ivosidenib could obtained 3185 € per month OS-gained with the normally applied discounts [15] and with a 38 220 € annual perspective, that is well below the cut-off [14].” (opens the source at this quote in a new tab)
“Another limit is related to the consideration of only the costs of drugs (which account for about 55% of total medical expenses).” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of first-line durvalumab added to gemcitabine and cisplatin from a United States payer perspective

“For US payers, the placebo plus chemotherapy group had a total cost of $56,157.05 and a utility of 1.10 QALYs, while the durvalumab plus chemotherapy group had a total cost of $217,069.25, a utility of 1.52 QALYs, resulting in an ICER of $381,864.39/QALY.” (opens the source at this quote in a new tab)
“For US payers, we set the willing to pay (WTP) threshold to $150,000/QALY.” (opens the source at this quote in a new tab)
“Both in China and in the US, durvalumab in combination with chemotherapy is not a cost-effective option for the first-line treatment of BTC compared with chemotherapy.” (opens the source at this quote in a new tab)

Cost-effectiveness analysis of first-line pembrolizumab added to chemotherapy from a United States payer perspective

“In the US, this treatment was not cost-effective, resulting in an improvement in effectiveness of 0.144 QALYs and an increase in overall cost of $141,000 (ICER of $976,925).” (opens the source at this quote in a new tab)
“In the US, the WTP threshold was set at $150,000” (opens the source at this quote in a new tab)

Budget impact model of lirafugratinib: approach and framework

No evidence found.

Model structures used in economic evaluations of advanced biliary tract cancer

“The progression-free health state was further divided into on-treatment and off-treatment substates. The EAG agreed that the structure of the economic model was appropriate and consistent with previous NICE evaluations for biliary tract cancer.” (opens the source at this quote in a new tab)

“In comparing medical costs and clinical outcomes between patients with BTC treated with pembrolizumab plus chemotherapy and those treated with chemotherapy, we used a partitioned survival model” (opens the source at this quote in a new tab)
“The health states included in this model were PFS, progressed disease (PD), and death.” (opens the source at this quote in a new tab)

“The model included three health states: PFS, progressive disease (PD) and death.” (opens the source at this quote in a new tab)

Model structures used in economic evaluations of FGFR inhibitors in cholangiocarcinoma

“This study used a 3-state partitioned survival model to analyze the 5 year cost-effectiveness of pemigatinib as a second-line treatment for advanced ICC patients in whom first-line gemcitabine-based chemotherapy failed and to compare the results with those for the mFOLFOX and 5-FU chemotherapy regimens.” (opens the source at this quote in a new tab)
“Overall survival and progression-free survival were estimated from the FIGHT-202 trial (pemigatinib), ABC-06 trial (mFOLFOX), and NIFTY trial (5-FU).” (opens the source at this quote in a new tab)

“We used a three-state partitioned survival model to evaluate the lifetime cost-effectiveness of pemigatinib compared to mFOLFOX or 5-FU/LV, based on data from the updated FIGHT-202, ABC-06, and updated NIFTY pivotal trials.” (opens the source at this quote in a new tab)
“As a result, we reconstructed survival curves from published KM curves and conducted a naïve indirect comparison, assuming comparability across the three trial populations.” (opens the source at this quote in a new tab)

“A partitioned survival model, with five health states, was locally adapted from a Greek payer perspective over a lifetime horizon.” (opens the source at this quote in a new tab)
“A matching-adjusted indirect comparison of pemigatinib and mFOLFOX+ASC was performed.” (opens the source at this quote in a new tab)

Model structure and inputs of the Taiwanese cost-effectiveness analysis of a biomarker-driven pemigatinib regimen

“To better reflect the current circumstances in Taiwan, the intervention regimen was pemigatinib for advanced ICC patients with FGFR2 fusions or rearrangements and mFOLFOX for those without FGFR2 fusions. The comparison regimen was 5-FU systemic therapy, one of the current regimens reimbursed by the NHI (Fig. 1).” (opens the source at this quote in a new tab)
“Patients with advanced intrahepatic cholangiocarcinoma receive genetic testing before starting second-line therapy.” (opens the source at this quote in a new tab)
“Overall and progression-free survival functions of pemigatinib, mFOLFOX, and fluorouracil were estimated from the FIGHT-202, ABC-06, and NIFTY trials, respectively.” (opens the source at this quote in a new tab)
“We decided to proceed with the PSMs on a 1-month cycle and with a follow-up for 5 years.” (opens the source at this quote in a new tab)
“health state utility values for progression-free status and progressed disease were 0.76 and 0.68, respectively, and assumed to be beta distributions.” (opens the source at this quote in a new tab)
“The proportions of adverse events ≥ grade 3 were 56%, 54%, and 18% in the pemigatinib arm, the mFOLFOX arm, and the 5-FU arm, respectively.” (opens the source at this quote in a new tab)

Model structures used in NICE appraisals of FGFR inhibitors in cholangiocarcinoma

“The company's partitioned survival model used parametric survival models to predict outcomes including time-on-treatment, progression-free survival and overall survival.” (opens the source at this quote in a new tab)
“It used a life-time horizon with a cycle length of 1 week. An annual discount rate of 3.5% was applied to costs and outcomes.” (opens the source at this quote in a new tab)

“The model cycle length was 21 days and a lifetime time horizon was used.” (opens the source at this quote in a new tab)

Use of FGFR inhibitors among patients with FGFR2 fusion-positive biliary tract cancer at academic centers

“In contrast, 80 (7.6%) of 1049 patients had a tumor with an FGFR2 fusion, and 64 (80%) were treated with FGFR inhibitors.” (opens the source at this quote in a new tab)

Numbers of patients starting futibatinib and pemigatinib in United States electronic medical records and claims, 2023 or later

“This study included 50 futibatinib and 55 pemigatinib patients.” (opens the source at this quote in a new tab)

“This study included 122 futibatinib (median age: 64 years; female: 58%; White: 66%) and 93 pemigatinib patients (median age: 66 years; female: 61%; White: 69%).” (opens the source at this quote in a new tab)

Uptake of pemigatinib assumed in the Canadian budget impact reanalysis

“In the CADTH reanalysis, the proportion of eligible patients who will use pemigatinib in year 1, 2, and 3 was changed to 80%, 85%, and 90%, respectively.” (opens the source at this quote in a new tab)

Uptake of futibatinib against pemigatinib assumed in the NICE resource impact assessment

Year	Uptake for futibatinib (%)
Current practice	“0”
2024-25	“40”
2025-26	“50”
2026-27	“50”

“The uptake for futibatinib is based on the NHS England expert opinion.” (opens the source at this quote in a new tab)
“The comparator treatment for the eligible population is pemigatinib.” (opens the source at this quote in a new tab)

Market share assumed for later-entrant oral targeted oncology agents in United States budget impact models

“Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib.” (opens the source at this quote in a new tab)

“With an assumed market share of approximately 6% for enzalutamide in year 1, the budget impact would be $106,074 ($0.009 per member per month [PMPM]). With a 26% enzalutamide share in year 3, the budget impact would be $632,729 ($0.048 PMPM).” (opens the source at this quote in a new tab)

“In the scenario with access to zanubrutinib, it is assumed uptake is 10% in year 1, followed by an increase of 5% in year 2 and year 3” (opens the source at this quote in a new tab)

“Market share for pirtobrutinib was assumed to be 39% in year 1 (year of pirtobrutinib approval) and 50% for years 2-5 (post approval).” (opens the source at this quote in a new tab)

Budget impact model of lirafugratinib: perspective and time frame

No evidence found.

Perspectives and time horizons used in economic evaluations of advanced biliary tract cancer

“Most cost-effectiveness studies adopted a healthcare-payer or healthcare-system perspective, while only a minority explicitly incorporated broader societal costs such as productivity loss.” (opens the source at this quote in a new tab)

“Hence, with reference to the dosing cycle of the TOPAZ-1 clinical trial, we set the cycle of the Markov model to 21 days and the time horizon of 10 years to simulate the entire life course of the patient” (opens the source at this quote in a new tab)
“This research was based on the perspective of Chinese and US payers, applying discount rates of 3% and 5% to costs and utilities, respectively” (opens the source at this quote in a new tab)

“This analysis adopted the health care perspectives of third-party payers in China and the US, respectively.” (opens the source at this quote in a new tab)
“In China, costs (converted to US dollars) and utilities were discounted at 5%, whereas in the United States, both costs and utilities were discounted at 3%” (opens the source at this quote in a new tab)

Perspectives, time horizons, and discount rates used in economic evaluations of FGFR inhibitors in cholangiocarcinoma

“A three-state partitioned survival model with a 5-year time horizon was constructed for patients with advanced intrahepatic cholangiocarcinoma who did not respond to first-line therapy.” (opens the source at this quote in a new tab)
“The willingness-to-pay threshold was three times the gross domestic product per capita in 2021 (NT$2,889,684).” (opens the source at this quote in a new tab)

“The willingness-to-pay threshold was three times the forecasted gross domestic product per capita in 2022 (NT$2,928,570).” (opens the source at this quote in a new tab)
“A 3% discount rate was applied to quality-adjusted life-years (QALYs) and costs.” (opens the source at this quote in a new tab)

“All future outcomes were discounted at 3.5% per annum.” (opens the source at this quote in a new tab)

“An ICER below the threshold of $50,000 is considered to have high value and is cost-effective, while an ICER above the threshold of $150,000 is considered to have low value and is not cost-effective.” (opens the source at this quote in a new tab)

Time horizon and willingness-to-pay threshold in the Taiwanese cost-effectiveness analysis of a biomarker-driven pemigatinib regimen

“To avoid overestimating clinical efficacy from extrapolating survival curves, we used a 5-year horizon instead of a lifetime horizon.” (opens the source at this quote in a new tab)
“Because there was no official WTP threshold in Taiwan, the WTP threshold was three times the gross domestic product per capita in 2021 (NT$2,889,684) recommended by the World Health Organization” (opens the source at this quote in a new tab)

Budget impact model of lirafugratinib: eligible population inputs

No evidence found.

Manufacturer estimate of the United States population with FGFR2-mediated cancers

“We believe FGFR2-mediated cancers affect approximately 11,000 late-line patients annually in the United States.” (opens the source at this quote in a new tab)
“In the future, if lirafugratinib advances to earlier lines of treatment, we believe it could potentially address approximately 35,000 patients annually in the United States.” (opens the source at this quote in a new tab)
“These numbers reflect the inclusion of patients with additional FGFR2 gene fusions and rearrangements that result from truncation of the protein at exon 18 based on recently published research suggesting that patients with these truncations should be considered for FGFR-targeted therapies.” (opens the source at this quote in a new tab)

Frequency of FGFR2 fusions or rearrangements used for eligible population sizing

“The FGFR2 fusions or rearrangements are found in 10% to 20% of patients with intrahepatic CCA, while they rarely occur in extrahepatic CCA.” (opens the source at this quote in a new tab)

“Of intrahepatic CCAs (iCCAs), ≤10% harbor fibroblast growth factor receptor-2 (FGFR2) fusions or rearrangements.” (opens the source at this quote in a new tab)
“this study is likely to have included patients with iCCA harboring FGFR2 alterations based on the reimbursement of pemigatinib, a subgroup that comprises ∼10%-15% of all iCCA cases” (opens the source at this quote in a new tab)

FGFR2 fusion prevalence and incidence inputs in the Taiwanese cost-effectiveness analysis

“According to the Taiwan Cancer Registry annual report, there were 1045 new incidences of ICC in 2019” (opens the source at this quote in a new tab)
“The proportion of FGFR2 fusions among Taiwanese patients was assumed to be 7.7% (beta distribution)” (opens the source at this quote in a new tab)
“Among patients with ICC, more than 90% did not have FGFR2 fusions, and therefore, the CEA result of using pemigatinib for patients with FGFR fusions in our study was highly dependent on the CEA of mFOLFOX for patients without FGFR2 fusions.” (opens the source at this quote in a new tab)

Eligible population assumptions in the Canadian budget impact reanalysis of pemigatinib

“CDA-AMC conducted a reanalysis that included: increasing pemigatinib uptake, changing the relative dose intensity to 100%, using the growth rate associated with intrahepatic CCA, removing market shares for clinical trials, assuming 85% of patients were diagnosed and unresectable and using component mFOLFOX prices sourced from DeltaPA.” (opens the source at this quote in a new tab)

Share of patients with advanced biliary tract cancer who reach second-line therapy in United States claims data

“Of 413 patients, 84.5% received gemcitabine-based first-line (1L) treatment, 46% received second-line treatment, and 16.5% received third-line (3L) treatment.” (opens the source at this quote in a new tab)

“A total of 514 patients (39.6%) died during the follow-up period without receiving a second-line therapy.” (opens the source at this quote in a new tab)

Incidence of intrahepatic cholangiocarcinoma in the SEER 22 registries, 2000 to 2020

“In this analysis of 28,918 iCCA patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 [annual percent change (APC) 6.94, 95% confidence interval (CI): 6.32 to 7.56], with a notable decline from 2019 to 2020.” (opens the source at this quote in a new tab)
“The AAIR per 100,000 was 0.49 (95% CI: 0.45–0.53) in 2000, 1.39 (95% CI: 1.33–1.44) in 2017, 1.32 (95% CI: 1.26–1.37) in 2018, 1.43 (95% CI: 1.38–1.49) in 2019, and 1.38 (95% CI: 1.32–1.43) in 2020.” (opens the source at this quote in a new tab)
“Incidence rates for 2000–2020 were age-standardized to the 2000 US population in 5-year age groups.” (opens the source at this quote in a new tab)

Age range and age adjustment of the SEER 18 incidence rates for cholangiocarcinoma

“Patients were at least 18 years old at diagnosis and had iCCA (ICD-O-3 topography code C22.1) or eCCA (ICD-O-3 topography codes C24.0, C24.1, and C24.9).” (opens the source at this quote in a new tab)
“Incidence rates (per 100 000 person-years [p-y]) were age-adjusted to the US Census bureau’s population for the year 2000.” (opens the source at this quote in a new tab)

Advanced disease, palliative systemic chemotherapy, and genomic profiling in intrahepatic cholangiocarcinoma at 8 United States centers

Measure in patients with intrahepatic cholangiocarcinoma	Value
Total number of patients with advanced disease (locally advanced, primary metastatic, recurrent metastatic)	“543 (88.9%)”
Treated with palliative systemic chemotherapy	“388/589 (65.9%)”

“Genomic profiling data were available for 64.3% (n = 349/543) of patients with advanced ICC and 50.3% (n = 92/183) of patients with advanced ECC (P < .001) (Figure 1).” (opens the source at this quote in a new tab)

Eligibility for resection at presentation and recurrence after resection

“Most patients with CCA have metastatic or locally advanced (that is, unresectable) disease at presentation, and only ∼25% are eligible for resection” (opens the source at this quote in a new tab)

“Despite the importance of surgical resection to overall prognosis, recurrence is common, occurring in up to 75% of patients after hepatectomy at 5 years, highlighting the importance of developing multimodality therapeutic approaches in order to improve the long-term outcomes for this aggressive cancer” (opens the source at this quote in a new tab)

Receipt of second-line therapy among patients with advanced cholangiocarcinoma and FGFR2 fusions or rearrangements in a United States clinico-genomic database

“This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine clinico-genomic database.” (opens the source at this quote in a new tab)
“As of May 2020, 571 patients met the inclusion criteria; 75 patients with FGFR2 fusions/rearrangements (median age 63 years; 64% female; 95% iCCA; 68% stage IV at initial diagnosis), and 496 patients with WT FGFR2 (median age 65 years; 48% female; 74% iCCA; 55% stage IV at initial diagnosis).” (opens the source at this quote in a new tab)
“50 patients with FGFR2 fusions/rearrangements (median age 62 years; 70% female; 94% iCCA; 70% stage IV at diagnosis) received second-line therapy.” (opens the source at this quote in a new tab)

Patients with intrahepatic cholangiocarcinoma and FGFR2 fusions evaluable for first-line and second-line treatment at one United States center

Treatment line	Evaluable patients with FGFR2 fusions, n
First-line treatment	“15”
Second-line treatment	“11”

Budget impact model of lirafugratinib: cost assumptions

No evidence found.

Drug acquisition cost of pemigatinib in Canada

“Treatment with Pemazyre is expected to cost, on average, $15,499 per 28 days (assuming 13.5 mg is administered orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles).” (opens the source at this quote in a new tab)

Drug acquisition cost of pemigatinib in Taiwan

“A 5-year cost-effectiveness analysis (CEA) conducted prior to reimbursement indicated that pemigatinib’s value-based price of NT$8,910 (US$286.04) per 13.5 mg was lower than the NHIA’s listing price of NT$12,500 (US$401.28), suggesting that the current listing price exceeds the estimated value-based price, making pemigatinib not cost-effective compared to systemic therapies with mFOLFOX or 5-FU/LV over 5 years” (opens the source at this quote in a new tab)
“The direct medical costs associated with the PD state primarily consist of supportive care expenses covered by the NHIA, totaling US$15,978 per year” (opens the source at this quote in a new tab)
“These costs are reported in 2023 U.S. dollars (1 USD = 31.35 TWD)” (opens the source at this quote in a new tab)

“The price of pemigatinib 13.5 mg was set at the potentially highest listing price (NT$17,820).” (opens the source at this quote in a new tab)
“The hypothesized medication cost of pemigatinib (NT$6600 × 3 × 0.9 = NT$17,820) was set at the potential highest listing price and assumed to be a uniform distribution” (opens the source at this quote in a new tab)

Drug acquisition cost of pemigatinib and futibatinib in England

“The list price of pemigatinib 13.5 mg tablets is £7,159.04 for a pack of 14 (company submission), which is an annual cost of £124,430. The company has a commercial arrangement. This makes pemigatinib available to the NHS with a discount. The size of the discount is commercial in confidence.” (opens the source at this quote in a new tab)

“The list price of futibatinib is £2,386.33 per pack containing 35, 28 or 21 4-mg tablets (excluding VAT, company submission).” (opens the source at this quote in a new tab)
“The company has a commercial arrangement. This makes futibatinib available to the NHS with a discount. The size of the discount is commercial in confidence.” (opens the source at this quote in a new tab)

Cost inputs and genetic testing fee in the Taiwanese cost-effectiveness analysis of a biomarker-driven pemigatinib regimen

“Genetic testing fees, medication costs for second-line therapy, and other medical expenses were included in the progression-free state; expenditure for supportive care was included in the disease-progressed state.” (opens the source at this quote in a new tab)
“Except for genetic testing (ACTFusion™, NT$30,000 on the date of the new treatment regimen [27]) and the cost of pemigatinib (NT$285,714 per month) set at the market price in 2021 and assumed to be uniform distributions, all other costs were estimated from the National Health Insurance Research Database (NHIRD) and assumed to be gamma distributions.” (opens the source at this quote in a new tab)
“For the progression-free state, the average costs per cycle of medication and other medical expenditures were NT$285,714 and NT$23,949 for pemigatinib users, NT$33,847 and NT$70,389 for mFOLFOX users, and NT$14,600 and NT$70,389 for 5-FU users, respectively. For the disease progression state, the average cost per cycle of supportive care was NT$37,518 for all patients.” (opens the source at this quote in a new tab)

Modelled lifetime cost per patient of pemigatinib and second-line comparators from a Greek payer perspective

“Total lifetime cost per patient with pemigatinib, mFOLFOX+ASC and ASC alone were estimated to be €85,534, €2,537 and €1,010 respectively.” (opens the source at this quote in a new tab)
“Reimbursable direct costs pertaining to drug acquisition, administration, monitoring, adverse events, and end of life were considered in the analysis.” (opens the source at this quote in a new tab)

Real-world United States health care cost per patient per month among patients treated with pemigatinib, claims data 2020 to 2023

“During the follow-up period, mean all-cause health care costs (PPPM) were $11 139, based on 2022 US dollars, with $8889 attributable to CCA-related care.” (opens the source at this quote in a new tab)
“The majority of all-cause health care costs were driven by ambulatory visits ($6464 PPPM) and inpatient stays ($3888 PPPM).” (opens the source at this quote in a new tab)
“During observation, 47.1% of patients discontinued pemigatinib; median [95% confidence interval (CI)] time to discontinuation was 7.0 (6.1-9.7) months.” (opens the source at this quote in a new tab)

United States monthly price of futibatinib, an FGFR inhibitor comparator

“The cost of drugs was obtained from www.pharmacychecker.com using the FDA label to determine the dosage and number of tablets required per day. This methodology excludes any private or governmental insurance coverage, which would cover the entire cost or more likely a fraction of the stated price.” (opens the source at this quote in a new tab)
“The average monthly cost for the treatment of neoplastic diseases was $17,900 with a price of $44,000 for futibatinib (used to treat cholangiocarcinomas with FGFR2 fusions) and minimum of $5100 for binimetinib (melanoma).” (opens the source at this quote in a new tab)
“We retrieved drug prices in November 2023 from www.pharmacychecker.com for the average patient living in the state of North Carolina (ZIP code 28791). These values represent the retail price of a drug at the pharmacy as determined by negotiations between pharmacies and insurers and reflect both wholesale and retail markups.” (opens the source at this quote in a new tab)
“Results from clinical trials do not favor one drug over the other [83]; the difference in pricing is thus unrelated to clinical efficacy.” (opens the source at this quote in a new tab)
“Infigratinib had also been approved for the treatment of this uncommon disorder, but the distribution of this FGFR inhibitor has been discontinued in the United States [84].” (opens the source at this quote in a new tab)

United States drug cost inputs per treatment cycle for regimens used in advanced biliary tract cancer

“Drug costs in the US, $/per cycle” (opens the source at this quote in a new tab)

Drug	Baseline cost in the United States, USD per cycle
Gemcitabine	“15.06”
Cisplatin	“8.72”
Durvalumab	“11,730”
Oxaliplatin	“26.76”
Calcium folinate	“52.48”
Fluorouracil	“18.57”
Irinotecan	“35.88”
Capecitabine	“180.6”
Regorafenib	“21,546”

Real-world United States cost per patient per month by line of therapy in advanced biliary tract cancer

“The mean PPPM costs for the overall population were $18,274 for all-cause costs, of which approximately 84% ($15,296) comprised BTC-related costs. The total mean (SD) PPPM all-cause costs by LOT were $19,589 ($22,603) for 1LOT, $22,617 ($19,302) for 2LOT and $33,534 ($40,588) for 3LOT.” (opens the source at this quote in a new tab)
“We found that total all-cause PPPM cost was $19,589 during 1LOT, increasing to $22,617 and $33,534 as the treatment advanced to 2LOT and 3LOT, respectively, with >80% of PPPM costs only related to BTC.” (opens the source at this quote in a new tab)

Real-world United States cost per patient per month after failure of first-line therapy for advanced cholangiocarcinoma

“Total mean per patient per month CCA-related healthcare costs were $7,743, with medical services ($6,685) a larger driver of monthly costs relative to treatment costs ($1,058).” (opens the source at this quote in a new tab)
“The total mean all-cause PPPM healthcare costs were $14,403.” (opens the source at this quote in a new tab)

Real-world United States cost per patient per month among patients treated with pemigatinib

“CUP was associated with significantly higher prevalence of metastatic disease (100.0% vs 63.6%), per patient per month (PPPM) ambulatory HCRU (8.2 vs 5.5), and ambulatory costs ($8584 vs $5308).” (opens the source at this quote in a new tab)
“Medical costs averaged $13 444 vs $9881 PPPM for CUP and non-CUP, respectively” (opens the source at this quote in a new tab)

Modelled lifetime treatment costs per patient in advanced biliary tract cancer from a United States payer perspective

“In China and the US, the cost of pembrolizumab plus chemotherapy was higher than that of chemotherapy alone ($85,480 versus $21,616, $297,282 versus $156,281).” (opens the source at this quote in a new tab)

Administration and monitoring cost assumptions for FOLFOX, the principal second-line chemotherapy comparator

“the committee concluded that the model should include a relative dose intensity of 78% for FOLFOX, and that relative dose intensity should be applied to both treatment acquisition and administration costs.” (opens the source at this quote in a new tab)
“At the second meeting, the company updated its model to include the NHS cost collection reference cost for all ECGs. This was £118. The EAG noted that this may be an overestimate and instead chose to use the cost for directly accessed diagnostic services only (£54).” (opens the source at this quote in a new tab)

Biomarker testing cost assumptions for biomarker-selected second-line comparators

“The clinical experts described that the cancer is screened for different genetic alterations at diagnosis to determine eligibility for targeted second-line treatment.” (opens the source at this quote in a new tab)
“The costs of additional IHC tests were included as part of the company submission.” (opens the source at this quote in a new tab)

“To the present costs we should add the cost of the IDH1 analysis (about 190 € for each patient [18]), that should be performed for all cholangiocarcinoma, with IDH1 mutation in approximately 20% of patients with intrahepatic cholangiocarcinoma [1]” (opens the source at this quote in a new tab)

FGFR2 testing cost and availability assumed in health technology assessments of pemigatinib

“The price reduction is influenced by the cost of testing, which is estimated to be $38,000 to identify a single patient eligible for treatment with pemigatinib.” (opens the source at this quote in a new tab)
“Availability of FGFR2 testing: pERC noted that the pharmacoeconomic reanalysis assumed that FGFR2 testing was not publicly funded without pemigatinib.” (opens the source at this quote in a new tab)
“Feedback from the sponsor indicated that FGFR2 testing is currently available and funded in Alberta and Ontario and may be provided on a case-by-case basis in Nova Scotia and New Brunswick.” (opens the source at this quote in a new tab)

“It was noted by the drug programs that FGFR2 testing is not routinely available nor funded in jurisdictions.” (opens the source at this quote in a new tab)

“The genetic testing fee and price of pemigatinib were set as the market price.” (opens the source at this quote in a new tab)

“The genetic testing fee was set at the market price and assumed to be uniform distribution.” (opens the source at this quote in a new tab)

FGFR2 testing and optical coherence tomography costs in the NICE appraisal of pemigatinib

“The prevalence of FGFR2 fusion or rearrangement is about 10% across all types of cholangiocarcinoma. So, adding FGFR2 as a target would incur an additional cost of £34, which would be applicable if pemigatinib is recommended for routine use in NHS practice. This gives a preferred cost of £340 for each additional person identified who is FGFR2-positive.” (opens the source at this quote in a new tab)
“The committee concluded that the costs of optical coherence tomography should be included in the economic analysis. After consultation, the company included the cost of optical coherence tomography in its analysis.” (opens the source at this quote in a new tab)

Time on treatment assumed in the NICE appraisal of futibatinib

“Respective median progression-free survival and median time on treatment were 8.9 months and 9.1 months for futibatinib and 6.9 months and 7.2 months for pemigatinib.” (opens the source at this quote in a new tab)
“So, the committee concluded that time on treatment should be the same for futibatinib and pemigatinib.” (opens the source at this quote in a new tab)

Placeholder price for a product without a published price in the ICER reference case

“3) If still not available and there are other similar drugs in the class, calculate the average net price across these drugs (using net pricing steps described in the section for branded treatments with a price available that do not require provider administration) and use that average as the placeholder price for the treatment;” (opens the source at this quote in a new tab)
“Regardless of specific approach, the price selected will be a placeholder price and should be identified as such throughout the review with clarifying text and footnotes to respective result displays.” (opens the source at this quote in a new tab)

Package sizes of pemigatinib and futibatinib in the United States labels

“in bottles of 14 with child-resistant closure” (opens the source at this quote in a new tab)

“20 mg daily dose: Each carton contains 1 blister card containing a 7-day supply (35 tablets; 4 mg futibatinib per tablet). [NDC-64842-0120-6]” (opens the source at this quote in a new tab)

Relative dose intensity of futibatinib in the FDA review of the pivotal trial

“Median relative dose intensity was 85.71%.” (opens the source at this quote in a new tab)

Duration of pemigatinib and futibatinib treatment in United States real-world studies

“Among all patients, the median DOT with pemigatinib was 7.4 months (95% CI: 6.2-8.8).” (opens the source at this quote in a new tab)

“median rwTTD was similar in both futibatinib and pemigatinib patients (2.8 vs. 2.8 months)” (opens the source at this quote in a new tab)

FOLFOX regimen, cycle length, and number of cycles received in ABC-06

“Patients allocated to the ASC plus FOLFOX group also received FOLFOX chemotherapy every 2 weeks for a maximum of 12 cycles.” (opens the source at this quote in a new tab)
“Treatment took place over 2 days, and consisted of oxaliplatin 85 mg/m2 (in 250–500 mL of 5% glucose; 2-h intravenous infusion), L-folinic acid 175 mg (or folinic acid 350 mg; 2-h intravenous infusion concurrently with oxaliplatin infusion), and fluorouracil 400 mg/m2 (5–10 min bolus) completed on day 1, and fluorouracil 2400 mg/m2 as continuous intravenous infusion starting on day 1 and finishing on day 2.” (opens the source at this quote in a new tab)
“The median number of FOLFOX cycles received was five (IQR 2–6), with a median interval between the first and last doses received of 70 days (41–111).” (opens the source at this quote in a new tab)

Grade 3 or 4 adverse reactions with pemigatinib in the United States label (N=146)

Adverse reaction	All grades (%)	Grades 3 or 4 (%)
Hypophosphatemia	“23”	“12”
Nail toxicity	“43”	“2.1”
Palmar-plantar erythrodysesthesia syndrome	“15”	“4.1”
Stomatitis	“35”	“5”
Fatigue	“42”	“4.8”
Arthralgia	“25”	“6”

Grade 3 adverse reactions and grade 3 or 4 phosphate decrease with futibatinib in the United States label (N=103)

Adverse reaction	All grades (%)	Grade 3 (%)
Nail toxicity	“47”	“1.9”
Palmar-plantar erythrodysesthesia syndrome	“21”	“4.9”
Stomatitis	“30”	“6”
Fatigue	“37”	“8”

Laboratory abnormality	All grades (%)	Grades 3 or 4 (%)
Decreased phosphate	“50”	“20”

Chemotherapy-related grade 3 to 5 adverse events with FOLFOX in ABC-06 (N=81)

“The most frequently reported grade 3–5 chemotherapy-related adverse events were neutropenia (ten [12%] patients), fatigue or lethargy (nine [11%] patients), and infection (eight [10%] patients” (opens the source at this quote in a new tab)

Chemotherapy-related adverse event	Grade 3	Grade 4	Grade 5
Fatigue or lethargy	“9 (11%)”	“0”	“0”
Neutropenia	“8 (10%)”	“2 (2%)”	“0”
Infection	“6 (7%)”	“1 (1%)”	“1 (1%)”
Febrile neutropenia	“0”	“1 (1%)”	“1 (1%)”

Site of care assumed for grade 3 or higher adverse events in United States cost models

“However, for certain AEs (eg, dermatologic events and laboratory abnormalities) management was assumed to occur in the outpatient setting only based on clinical expert input indicating that these events, even at Grade ≥3 severity, do not routinely require inpatient admission.” (opens the source at this quote in a new tab)

“As patients with grade 3/4 AEs require hospitalization based on the definitions by Common Terminology Criteria for Adverse Events (CTCAE), the national level of inpatient costs from the HCUP database were used to estimate the unit costs associated with each grade 3/4 AE.” (opens the source at this quote in a new tab)
“All costs were inflated to 2020 US dollars (USD) using an inflation factor of 1.0793 from 2017 USD based on the Consumer Price Index (CPI) for all urban consumers in medical care service.” (opens the source at this quote in a new tab)

United States cost per adverse event from claims of patients treated with VEGFR tyrosine kinase inhibitors, 2015 to 2021

“A sum of all claims associated with the AE diagnosis code during the 90 days following the index AE (including index AE), contributed to cost.” (opens the source at this quote in a new tab)
“The least costly AEs were proteinuria and fatigue, with an average total cost of $76 and $416 respectively over the 90-day timeframe, while the costliest were mucositis ($1687 average), diarrhea ($1371 average), and rash ($1370 average).” (opens the source at this quote in a new tab)

Adverse event	Average cost per patient with the adverse event
Palmar-plantar erythrodysesthesia or hand-foot skin reaction	“$1,316”
Mucositis or stomatitis	“$1,687”
Asthenia or fatigue	“$416”

United States hospitalization cost per grade 3 or 4 adverse event, 2020 United States dollars

Adverse event	Unit cost
Arthralgia	“$6513”
Palmar-plantar erythrodysesthesia syndrome	“$6480”
Stomatitis	“$8930”
Fatigue	“$7979”

United States cost of neutropenia, febrile neutropenia, and infection

Adverse event	Cost in the United States, USD
Neutropenia	“5,321.00”

“For adults, the mean length of stay for cancer-related neutropenia hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay.” (opens the source at this quote in a new tab)
“All costs are in 2012 US dollars.” (opens the source at this quote in a new tab)
“ranged from $12,689 to $27,587” (opens the source at this quote in a new tab)

Resource	Cost, 2014 United States dollars
Cellulitis, mean inpatient cost per hospitalization	“17,230”
Neutropenia, outpatient management	“2087.69”
Infection, outpatient management	“112.65”

Outpatient cost of hand-foot syndrome and fatigue in a United States cost-effectiveness analysis, 2014 United States dollars

Adverse event	Baseline cost, USD
Hand-foot syndrome	“134.48”

“Fatigue was assumed to have no specific medical management.” (opens the source at this quote in a new tab)
“Only direct medical costs were considered and stated in 2014 US dollars.” (opens the source at this quote in a new tab)

Serum phosphate testing schedule in the pivotal trial of futibatinib

“Serum phosphate levels were measured on days 1, 4, 8, and 15 of cycle 1 and on day 1 of every cycle thereafter.” (opens the source at this quote in a new tab)

Budget impact model of lirafugratinib: model outcomes

No evidence found.

Outcomes reported by economic evaluations in advanced biliary tract cancer

“For cost-effectiveness and cost–utility studies, we extracted ICERs, QALYs, life-years, total and incremental costs, willingness-to-pay thresholds, and the probability of cost-effectiveness where available.” (opens the source at this quote in a new tab)
“For cost-of-illness and resource-use studies, we extracted mean or median costs, cost categories, healthcare utilization, hospitalizations, treatment-line costs, productivity outcomes where reported, and principal cost drivers.” (opens the source at this quote in a new tab)

“Costs, life years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured and compared.” (opens the source at this quote in a new tab)

Outcomes reported by economic evaluations of FGFR inhibitors in cholangiocarcinoma

“Primary outcomes were patients’ life years (LYs), quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs) per QALY and LY gained.” (opens the source at this quote in a new tab)

“The primary measure was the incremental cost-effectiveness ratio (ICER).” (opens the source at this quote in a new tab)

Outcomes of the Taiwanese cost-effectiveness analysis of a biomarker-driven pemigatinib regimen

“In our study, the incremental cost-effectiveness ratio was calculated as the incremental cost per additional QALY between the new pemigatinib/mFOLFOX treatment regimen and the current 5-FU treatment in Taiwan. The incremental net monetary benefit (INMB) was calculated as the net monetary benefit of the new treatment regimen over current 5-FU treatment.” (opens the source at this quote in a new tab)

Budget impact model of lirafugratinib: base-case results

No evidence found.

Base-case results of United States cost-effectiveness analyses in advanced biliary tract cancer

“ICER was US $381,864/QALY from the US payer perspective and US $367,609/QALY from the Chinese payer perspective.” (opens the source at this quote in a new tab)
“PPPM all-cause costs increased across treatment lines: 1L US $19,589, 2L US $22,617, and 3L US $33,534” (opens the source at this quote in a new tab)
“Mean cost per patient-month was US $7743 (medical services US $6685; drug costs US $1058); median OS was 5.3 months” (opens the source at this quote in a new tab)

“In the US, this treatment was not cost-effective, resulting in an improvement in effectiveness of 0.144 QALYs and an increase in overall cost of $141,000 (ICER of $976,925).” (opens the source at this quote in a new tab)

Base-case budget impact of pemigatinib in Canada

“Based on public list prices, Pemazyre is estimated to cost the public drug plans approximately $64 million over the next 3 years. However, the actual budget impact is uncertain.” (opens the source at this quote in a new tab)
“Based on the CDA-AMC reanalyses, the budget impact from the introduction of pemigatinib is expected to be $18,571,801 in year 1, $21,113,817 in year 2, and $23,920,712 in year 3 for a 3-year total of $63,606,331.” (opens the source at this quote in a new tab)
“This is likely an underestimation of the true budget impact, as costs for patients who remain on pemigatinib for more than 1 year are not captured.” (opens the source at this quote in a new tab)

Base-case cost-effectiveness of pemigatinib in Canada

“In CDA-AMC reanalyses, the incremental cost-effectiveness ratio for pemigatinib relative to ASC alone and mFOLFOX plus ASC was estimated to be $252,718 and $261,226 per quality-adjusted life-year (QALY) gained, respectively, using the sponsor-submitted price for pemigatinib and publicly listed price for all other drugs.” (opens the source at this quote in a new tab)
“Pemigatinib was therefore not considered cost-effective at a $50,000 per QALY gained willingness-to-pay threshold.” (opens the source at this quote in a new tab)

Base-case cost-effectiveness of pemigatinib from the Taiwanese payer perspective

“Pemigatinib was associated with a 0.59 QALY increase with incremental costs of NT$3,428,442 and a 0.68 QALY increase with incremental costs of NT$3,653,100, yielding an ICER of NT$5,814,700 per QALY and an ICER of NT$5,380,241 per QALY compared to mFOLFOX and 5-FU, respectively (Table 2).” (opens the source at this quote in a new tab)

“Based on the updated efficacy data from pivotal trials, the base-case CEA results over a lifetime (Table 2) showed that compared to mFOLFOX, pemigatinib resulted in an incremental QALY of 1.20, additional costs of US$99,762, and an ICER of US$83,475 per QALY.” (opens the source at this quote in a new tab)
“Compared to 5-FU/LV, pemigatinib had an incremental QALY of 1.27, additional costs of US$107,186, and an ICER of US$84,386 per QALY.” (opens the source at this quote in a new tab)
“Both ICERs were below the WTP threshold (US$97,048), with INMB values of US$16,221 (mFOLFOX) and US$16,083 (5-FU/LV).” (opens the source at this quote in a new tab)

“The new regimen provided an incremental 0.13 quality-adjusted life-years, with incremental costs of NT$459,697, yielding an incremental cost-effectiveness ratio of NT$3,411,098 per quality-adjusted life-year and an incremental net monetary benefit of - NT$70,268.” (opens the source at this quote in a new tab)

Base-case costs and outcomes of the Taiwanese cost-effectiveness analysis of a biomarker-driven pemigatinib regimen

Estimate, 2021 NT$	Current regimen (fluorouracil)	New regimen (pemigatinib or mFOLFOX by FGFR2 status)
Total cost	“524,472”	“984,168”
Genetic testing fee	“0”	“30,000”
Medication cost	“63,430”	“387,176”
Non-medication cost	“305,799”	“378,437”
Total cost of progressed disease state	“155,243”	“188,555”

Outcome	Current regimen (fluorouracil)	New regimen (pemigatinib or mFOLFOX by FGFR2 status)	Incremental change
Life-years, overall	“0.67”	“0.86”	“0.19”
QALYs, overall	“0.47”	“0.61”	“0.13”

“The new regimen was found to be 53.2% cost effective in the probabilistic sensitivity analysis. The expected value of uncertainty measured by the expected value of perfect information was NT$80,695/person.” (opens the source at this quote in a new tab)

Base-case cost-effectiveness of pemigatinib from Greek and United States perspectives

“Furthermore, pemigatinib appeared to yield more QALYs gained versus mFOLFOX+ASC and ASC alone (1.66 vs 0.44 and 0.41, respectively), resulting in ICERs of €69,928 per QALY gained and €46,626 per LY gained versus mFOLFOX+ASC and €69,345 per QALY gained and €45,935 per LY gained compared to ASC alone.” (opens the source at this quote in a new tab)

“We calculated pemigatinib’s PFS ICER to be $127,127 and OS ICER to be $183,628.” (opens the source at this quote in a new tab)

Budget impact model of lirafugratinib: scenario analyses

No evidence found.

Sensitivity and scenario analyses in economic evaluations of advanced biliary tract cancer

“Sensitivity analysis showed that the analysis was most sensitive to the price of durvalumab.” (opens the source at this quote in a new tab)

“In China and the US, the ICER for pembrolizumab plus chemotherapy compared with that of chemotherapy alone was $535,405/QALY and $1,118,607/QALY.” (opens the source at this quote in a new tab)
“The results of the subgroup analysis indicate that better survival properties subgroups were more likely to be cost-effective, although pembrolizumab plus chemotherapy may not be cost-effective for all subgroups.” (opens the source at this quote in a new tab)

“PSA showed price cuts (~50–60%) needed” (opens the source at this quote in a new tab)
“A price reduction of at least approximately 50% improved cost-effectiveness results.” (opens the source at this quote in a new tab)
“In the economic models, the cost of the immune-checkpoint inhibitor component was repeatedly identified as a major driver of unfavorable cost-effectiveness results.” (opens the source at this quote in a new tab)

Price reductions required for cost-effectiveness of pemigatinib in Canada

“Price reductions exceeding 95% would be required for pemigatinib to achieve an incremental cost-effectiveness ratio of $50,000 per QALY gained.” (opens the source at this quote in a new tab)
“If testing costs were $0, a price reduction of 77% (versus ASC alone) and 72% (versus mFOLFOX and ASC) would be required to achieve cost-effectiveness at a willingness-to-pay per QALY gained of $50,000.” (opens the source at this quote in a new tab)

Budget impact scenarios for pemigatinib in Canada

“If 100% of patients have public coverage for pemigatinib, the expected 3-year budget impact will increase to $79,507,913.” (opens the source at this quote in a new tab)
“If pemigatinib was available at a 95% price reduction, the expected budget impact will be much lower at $979,163 over 3 years.” (opens the source at this quote in a new tab)

Price and time-horizon scenarios for pemigatinib from the Taiwanese payer perspective

“When the price of pemigatinib was reduced by 50% or more, pemigatinib gained a positive net monetary benefit (mFOLFOX: NT$55,374; 5-FU: NT$92,437) and a 72% (mFOLFOX) and 77.1% (5-FU) probability of being cost-effective.” (opens the source at this quote in a new tab)
“One-way sensitivity analysis indicated that the medication cost of pemigatinib, the utility of the PF state and the PD state, and the parameters of OS were the most crucial parameters influencing the results in both CEAs (Fig. 2a, b).” (opens the source at this quote in a new tab)

“Our study indicates that pemigatinib would not be cost-effective over short time horizons, such as 2 and 5 years (Scenario 1).” (opens the source at this quote in a new tab)
“Lifetime break-even analysis shows that pemigatinib reaches the breakeven point in the 8th year, a benefit not evident within shorter time horizons.” (opens the source at this quote in a new tab)
“Over 80% of incremental costs of pemigatinib incurred during the PF state.” (opens the source at this quote in a new tab)

“In scenario analyses, the incremental net monetary benefit was positive when the price of pemigatinib was reduced by 40% or more.” (opens the source at this quote in a new tab)

Price and model scenarios in the Taiwanese cost-effectiveness analysis of a biomarker-driven pemigatinib regimen

“The deterministic sensitivity analysis revealed that the utility of the progression-free state, the drug cost of pemigatinib, the drug cost of mFOLFOX, and the utility of the progressed disease state played vital roles in the CEA results (Fig. 2).” (opens the source at this quote in a new tab)
“The scenario analysis showed that the CEA was not sensitive to the change in the survival distribution function, while using log-logistic distributions for all PFS curves and OS curves slightly increased the probability of being cost effective to 55.1% (Fig. 4). The price scenario showed that the new regimen was cost effective with a probability of more than 60% and gained a positive INMB when the price of pemigatinib was reduced by 40% (Fig. 4).” (opens the source at this quote in a new tab)
“The probability that the new regimen is cost effective would be 76.4% if effectiveness was considered in life-years instead of QALYs (Fig. 4). When assuming adverse events incurred every cycle during the first 6 months and over the entire time horizon, the probability of the new regimen being cost effective dramatically reduced to 41% and 36.3%, respectively (Fig. 4).” (opens the source at this quote in a new tab)
“Most of the uncertainty came from utilities and drug costs; the expected value of perfect information showed that the new regimen with pemigatinib/modified FOLFOX had a relatively low opportunity cost.” (opens the source at this quote in a new tab)

Scenario	ICER, NT$ per QALY	INMB, NT$	Probability of being cost-effective
Base case	“3,411,098”	“-70,268”	“53.2%”
90% price of pemigatinib	“3,252,339”	“-48,873”	“54.9%”
80% price of pemigatinib	“3,093,579”	“-27,478”	“56.3%”
70% price of pemigatinib	“2,934,819”	“-6,083”	“59.3%”
60% price of pemigatinib	“2,776,060”	“15,313”	“62.6%”
50% price of pemigatinib	“2,617,300”	“36,708”	“66.0%”

Summary

No budget impact model of lirafugratinib has been published and no price has been announced, so its budget effect cannot be estimated from public evidence. The population inputs a payer would need are available in part: about 8,000 people in the United States are diagnosed with bile duct cancer each year, FGFR2 fusions or rearrangements occur in 10% to 16% of intrahepatic cholangiocarcinomas and in approximately 9% of profiled cholangiocarcinomas, 46% of participants with advanced biliary tract cancer in one United States claims cohort initiated second-line therapy, and Relay Therapeutics estimated approximately 11,000 late-line United States patients annually with FGFR2-mediated cancers of any tumour type.

Comparator costs are partly public. A United States retail price of $44,000 per month has been reported for futibatinib, and Canada's Drug Agency estimated pemigatinib at $15,499 per 28 days, with a 3-year public budget impact of $63,606,331 that it considered an underestimate because costs beyond 1 year of treatment were not captured. In England, NICE reports list prices of £7,159.04 for a pack of 14 pemigatinib 13.5 mg tablets, an annual cost of £124,430, and £2,386.33 per pack of futibatinib, both supplied at confidential discounts, and assumed the same time on treatment for futibatinib and pemigatinib. Real-world all-cause health care costs among United States participants treated with pemigatinib were $11,139 per patient per month, and all-cause costs during second-line therapy for advanced biliary tract cancer were $22,617 per patient per month.

Three features of lirafugratinib bear on a budget model. Treatment continues until progression and median progression-free survival in the pivotal cohort was 11.3 months, against 7.0 months for pemigatinib and 9.0 months for futibatinib in their pivotal trials, so drug cost per treated patient depends on duration as well as price. Required ophthalmologic examinations with optical coherence tomography occur every 2 months for 13 months and every 4 months thereafter, compared with every 2 months for 6 months and every 3 months thereafter for the comparators. FGFR2 testing costs are material: the Canadian estimate was about $38,000 per eligible patient identified, NICE estimated £340 for each additional FGFR2-positive person identified by adding FGFR2 to the NHS panel test, a Taiwanese model applied a genetic testing fee of NT$30,000, and the lirafugratinib companion diagnostic had not yet been specified in labeling at approval.