Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report submitted by the manufacturer of lecanemab (Eisai K.K.) on the additional benefits and cost-effectiveness of lecanemab for patients with mild cognitive impairment and mild dementia due to Alzheimer's disease. This report summarizes the results of a review and reanalysis conducted by the ATAG. In assessing additional benefits, the manufacturer referred to the results of subgroup analyses of mild cognitive impairment and mild dementia due to Alzheimer's disease and of patients with and without concomitant use of symptom-modifying drugs, in addition to the results of the overall population of the primary study, Study 301. The manufacturer reported that the primary endpoint, the change in the CDR-SB from baseline to 18 months, showed that, compared with placebo, lecanemab significantly reduced deterioration. In addition, the results of the subgroup analyses of mild cognitive impairment and mild dementia due to Alzheimer's disease and of patients treated with and without symptom-modifying drugs were not heterogeneous with the results of the overall population. On the basis of these findings, the manufacturer reported additional benefits of lecanemab in the following target populations: (a) mild cognitive impairment due to Alzheimer's disease and (b) mild Alzheimer's dementia. The ATAG accepted the manufacturer's claim of additional benefits on the basis of these results but considered with concern that the treatment efficacy of lecanemab observed in Study 301 was less than the minimal clinically important difference for the CDR-SB. In addition, the comparator in the target population (b) was donepezil, whereas the comparator in Study 301 was placebo, and since donepezil was not administered to the entire population, the ATAG speculated that in the specified analysis framework, the treatment efficacy would move in the direction of being smaller than that observed in the clinical trials. For the cost-effectiveness analysis, the manufacturer used a Markov model consisting of nine health states that considered the Alzheimer's disease severity, care setting, and death. In the model, the proportion of patients receiving lecanemab decreased at a constant rate over time, but the effect of reducing the severity of disease as a group was extrapolated directly, regardless of the proportion of patients receiving lecanemab. Therefore, even if the administration rate decreased, the difference in efficacy increased. In addition, while the efficacy after a patient moved to moderate disease was assumed to be equivalent to that of patients with mild disease, in the companyfs model, the administration of lecanemab was discontinued once the patient moved to moderate disease. In addition, the companyfs model set the mortality rates by severity on the basis of observational studies and assumed that patients in the lecanemab group with a prolonged duration of mild cognitive impairment or mild Alzheimer's disease would have prolonged survival. The academic group conducted a reanalysis using a newly constructed model. In the manufacturer's method for estimating the QALYs of family caregivers, the absolute utility values of the caregivers were used rather than the decrement in their quality of life. However, this approach effectively includes QALYs for both the patient and the caregiver. Therefore, in the academic analysis, the QALY gain was calculated based on the decrement in the caregiver's quality of life, rather than their absolute utility value. In addition to the above estimates of the effectiveness of lecanemab, issues were raised regarding the settings of utility weights for patients and caregivers and the method of estimating costs. The results of the base-case analysis using the model originally constructed by the ATAG, from the perspective of public healthcare and long-term care payer in Japan, revealed that the incremental costeffectiveness ratios (ICERs) of lecanemab compared to the comparator in target populations (a) and (b) were 15,388,842 yen/QALY and 16,703,239 yen/QALY, respectively. Sensitivity analysis revealed that the ICER of lecanemab exceeded JPY10,000,000/QALY in all cases. These results suggest that the ICERs for lecanemab for mild cognitive impairment and mild dementia due to Alzheimer's disease are likely to be in the range of more than 10 million yen/QALY from the perspective of public healthcare payers in Japan.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/en/results/C2H2308.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com