Lyrfigtu / Lirafugratinib for Unresectable or Metastatic Cholangiocarcinoma

As of October 2026, MARA’s assessment finds Lyrfigtu / Lirafugratinib’s reimbursement risk concentrated in safety and adverse effects, with patient population and subgroups a strength; the current MARA Rating and full rationale are available in the report.

The assessment also weighs clinical effectiveness: how much additional benefit the drug demonstrated over the care patients already receive — the first question every payer asks. The strength recorded in patient population and subgroups carries weight because that domain asks how closely the trial population matches the patients who would receive the drug in practice; payers often restrict funding to the groups where the evidence is strongest.

Oncology

This rating sits within MARA’s Oncology coverage, alongside 153 other independently assessed treatments in the same area.

What payers will ask

Is the clinical benefit the kind payers reward? — Clinical effectiveness

The evidence shows a competitive descriptive response signal with an ORR of 46% and median DOR of 11.8 months. However, the absence of randomization and lack of comparative data against standard of care or competitors limits the ability to establish a clear clinical advantage.

Does the economic case hold at the expected price? — Cost effectiveness

No economic model, ICER, or cost-effectiveness analysis is presented in the available evidence, making it not assessable.

Is there quality-of-life evidence payers weigh? — Quality of life

No detailed HRQoL data is reported. The available evidence mentions the use of EORTC QLQ-C30 but lacks domain scores, completion rates, or changes from baseline, making it impossible to assess HRQoL impact.

Does the safety profile hold up for payers? — Safety and Adverse Effects

The treatment is associated with frequent and severe adverse events, including palmar-plantar erythrodysesthesia and stomatitis. The high incidence of severe mucocutaneous events and dose modification requirements reduce the safety profile.

Was the drug compared against what payers expect? — Comparator Selection

The study is a single-arm phase 1/2 trial with no comparator arm. As per the rules, comparator selection is not assessable for phase-1-only programs.

Is the population defined the way payers need it? — Patient Population and Subgroups

The trial population is moderately representative of the target population, with strong molecular alignment but weak racial diversity and representativeness for frailer patients.

Does the drug fit how care is delivered and paid for? — Care Pathway Integration

The treatment requires significant monitoring and diagnostic processes, including ophthalmologic exams and molecular testing, which may impact integration into existing care pathways.

Are the wider system costs understood? — Resource Use and Cost Implications

No budget-impact or resource-use information is presented, making it not assessable.

Would the evidence survive payer scrutiny? — Evidence Quality and Robustness

The evidence is based on a single-arm phase 1/2 study with no control arm and incomplete public disclosure of protocol details, limiting the robustness and reproducibility of the findings.

How exposed is the case to uncertainty? — Uncertainty, Sensitivity, and Broader Impacts

High uncertainty exists due to the lack of comparative data, missing quantitative PRO results, and unresolved dose–toxicity uncertainty. The absence of sensitivity analysis further contributes to the uncertainty.

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