The social value of lecanemab for patients with early Alzheimer's disease in Japan

Abstract

Background

Lecanemab is the first approved disease-modified therapy in Japan for patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild AD dementia (AD-D).

Objective

This study aims to evaluate the social value of lecanemab in Japan.

Methods

The social value was evaluated using a cost-effectiveness model. The intervention was lecanemab added to the standard of care (SOC), and the comparator was SOC alone. The effect of lecanemab was determined based on the phase III trial and subsequent long-term follow-up observation studies. Health outcomes were quantified in life years and quality-adjusted life years (QALYs). Both patient and caregiver utilities were considered by summing the absolute values of utility for both the caregiver and patient. The base-case analysis was conducted from the public healthcare and long-term care payer's perspectives.

Results

Lecanemab extended the time spent in early AD, thereby maintaining quality of life (QOL), reducing caregiver burden, and medical and long-term care resource usage. The incremental QALYs were 1.31 QALYs for MCI due to AD and 0.85 QALYs for mild AD-D, and the incremental cost-effectiveness ratios (ICERs) were JPY 8.5 million /QALY and JPY 7.9 million /QALY ($1 = JPY 150), respectively.

Conclusions

The value-based price or the ICER of lecanemab varied greatly depending on the perspectives and the methods of reflecting caregiver QOL. In AD, where the progression of the illness spans a long period and had a significant impact on families and society, narrowly defined value assessments were not sufficient, indicating the need to consider broader social value.

Keywords

Alzheimer's disease caregivers caregiver burden cost-benefit analysis cost-effectiveness analysis lecanemab

Introduction

Alzheimer's disease (AD) is the leading cause of dementia, accounting for approximately 60% of all dementia cases¹ worldwide and 67.6% of dementia in Japan.² AD progresses from normal cognition to mild cognitive impairment (MCI), followed by dementia stages.³ As the disease advances, patients increasingly require assistance with daily functions, which significantly affects not only their own quality of life (QOL), but also that of their caregivers, who are often family members.⁴ Moreover, AD imposes a substantial economic burden on both, healthcare and long-term care systems.

In Japan, the annual medical cost associated with AD is estimated at JPY 1073 billion, while public long-term care costs reach approximately JPY 4783 billion.⁵ Additionally, informal care provided by family and friends is estimated to cost JPY 6772 billion annually.⁵ These costs are driven by factors such as dementia severity, patient dependence, cognitive and functional decline, institutionalization, comorbidities, treatment status, age, and behavioral symptoms.⁶ In Japan, the Basic Act on Dementia was enacted in January 2024 to promote the realization of an inclusive society. With the enforcement of the Basic Act on Dementia, various initiatives are expected to be undertaken towards the realization of a society wherein people with dementia and their families can live peacefully.

Lecanemab is a humanized monoclonal antibody (IgG1) and was the first approved treatment for patients with MCI due to AD, and mild AD. Clarity AD (NCT03887455) was a randomized, double-blind, placebo-controlled, phase 3 clinical study, evaluating the long-term efficacy and safety of intravenous lecanemab (10 mg/kg) every two weeks for early AD. The study was conducted over a period of 18 months, followed by an open-label extension (OLE) phase for up to 48 months.^7,8 The primary endpoint was the change from baseline at 18 months in the Clinical Dementia Rating Sum of Boxes (CDR-SB). The results of this study demonstrated that lecanemab was effective in slowing the rate of disease progression and reducing cognitive and functional decline.

Previous cost-effectiveness analyses of lecanemab, such as those conducted by Igarashi et al., suggested that combining lecanemab with the standard of care (SOC) could improve health outcomes while reducing the economic burden on patients and caregivers in Japan.⁹ The study by Igarashi et al., published in March 2023—prior to lecanemab's regulatory approval and pricing negotiations—was unprecedented in Japan, as it marked the first instance of a company proactively disclosing value-related evidence that could influence pricing.⁹ Amid rising concerns over high-cost therapies, this early presentation of lecanemab's value was timely and significant. However, as the authors noted, the analysis relied solely on 18-month randomized-controlled trial (RCT) data, with no information on long-term efficacy or real-world outcomes, necessitating several assumptions.

On December 13, 2023, lecanemab was selected for evaluation under Japan's health technology assessment (HTA) system.¹⁰ Given the unique characteristics of dementia, the inclusion of public long-term care costs was exceptionally permitted in the HTA analysis. This evaluation was conducted under a special measure, known as the “LEQEMBI Special Measure” delegated from Chuikyo. This measure allowed us to consider a broader perspective for the analysis, including public long-term care costs and caregiver QOL, and add new rules to reflect the results of price adjustments.¹¹ Evaluations were conducted from the perspectives of both, the public healthcare as well as the combined healthcare and long-term care payers. However, drug price revision, based on cost-effectiveness evaluation results, from the perspective of the former, excluding long-term care costs, was proposed and approved at Chuikyo.¹²

This study aimed to evaluate the social value and the benchmark price of lecanemab, following its market introduction, in the Japanese context. Employing a comprehensive cost-effectiveness framework, the analysis was conducted from three distinct perspectives, that of: (1) the public healthcare payer, which analysis included only direct medical costs as the costs, (2) the integrated healthcare and long-term care payer, which analysis included both direct medical costs and long-term care costs covered by the national insurance, and (3) the broader society encompassing informal caregiving provided by family caregivers without paying rewards. In line with the principles outlined in Japan's Dementia Basic Act, particularly its vision of realizing “an inclusive society,” this analysis included not only direct medical and public long-term care costs, but also the costs pertaining to informal care as well as caregiver and patients’ QOL. In particular, caregivers’ QOL was included in all three analyses, i.e., from the perspectives of the healthcare payer, public care payer, and the society, to reflect their important roles and social and financial impacts in the care of AD.

Additionally, because there is no standardized methodology for including caregivers’ QOL in cost-effectiveness analyses, we conducted scenario analyses for both, the traditional decrement approach, which uses the difference between QOL values of healthy controls, and the more recent NICE-endorsed increment approach. This attempt to present the multifaceted social value of lecanemab as evidence, which cannot be fully captured within the framework of Japan cost-effectiveness evaluation system.

Methods

Overview

In this study, the social value and the benchmark price of lecanemab were evaluated using a cost-effectiveness approach. The target population for the analysis included patients with early AD (MCI due to AD) or mild AD dementia (AD-D) with a confirmed amyloid-β (Aβ) pathology. The intervention and comparator were set up in accordance with Clarity AD.⁷ The intervention was lecanemab administered every two weeks at a dose of 10 mg/kg added to the SOC, and the comparator was SOC alone, which was assumed to consist of symptomatic and non-pharmacological treatments.

This study was conducted from the perspectives of the public healthcare and long-term care payers as a base-case analysis because dementia impacts long-term care costs more significantly than healthcare costs. In other words, the base-case analysis included the public direct medical and long-term care costs, while the public direct medical costs only from the public healthcare payer's perspective and the informal care costs from the societal perspective were added in the scenario analyses (Table 1).

Table 1.

Overview of analysis perspectives, included costs, and utilities.

Analysis	Perspective	Included costs	Included utilities
Base-case	Public Healthcare and Long-term Care Payer	Public medical costs Public long-term care costs	Patient utility Caregiver utility (Combined)*
Scenario (perspective)	Public Healthcare Payer	Public medical costs	Patient utility Caregiver utility (Combined)
Scenario (perspective)	Societal	Public medical costs Public long-term care costs Informal care costs	Patient utility Caregiver utility (Combined)
Scenario (caregiver utility)	Public Healthcare and Long-term Care Payer	Public medical costs Public long-term care costs	Patient utility Caregiver utility(decrement method)
	Public Healthcare and Long-term Care Payer	Public medical costs Public long-term care costs	Patient utility Caregiver utility(Increment method)
	Public Healthcare and Long-term Care Payer	Public medical costs Public long-term care costs	Patient utility (Patient-only; excluding caregiver utility)

* For caregiver utility, the combined approach was used in the base-case, while other methods (decrement, increment, and patient-only) were examined in scenario analyses.

An effective lifetime horizon of up to 30 years was used to capture the differential costs and outcomes over an individual's lifetime. Health outcomes were quantified in terms of life years and quality-adjusted life years (QALYs). Costs and QALYs were discounted by 2% annually. The costs were based on the 2024 Japanese fee schedule and drug tariffs, each defined by the MHLW at an exchange rate of USD 1 = JPY 150 (December 2024), as reported by the Bank of Japan.¹³ This analysis is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Model structure

A Markov state transition model, with health states based on disease severity, institutionalization, and death, was developed to evaluate the social value and the benchmark price of lecanemab (Figure 1). The model included the following nine health states to capture disease progression in patients across both, community and institutional settings, aligned with previously reported cost-effectiveness models for interventions in AD^14–17: MCI due to AD (community and institution), mild AD-D (community and institution), moderate AD-D (community and institution), severe AD-D (community and institution), and death. The model used a monthly cycle. Patients entered the model in either the “MCI due to AD” or “mild AD-D” health state. All patients were assumed to enter the model in the community setting. Patients could transition between health states, including disease severity levels and care settings, or could die during each model cycle. In addition to health-state transitions, the risk of discontinuation was also considered. Discontinuation of lecanemab was assumed to occur due to all-cause discontinuation, as observed in Clarity AD,⁸ when a patient transitioned to a moderate AD-D health state or was institutionalized. Adverse events modeled included amyloid-related imaging abnormalities with edema (ARIA-E) and isolated amyloid-related imaging abnormalities with hemosiderin (ARIA-H), which are more likely to occur when a patient initiates treatment with lecanemab; the costs of these were applied as a one-off upfront cost.

Figure 1.

Model structure. AD: Alzheimer's disease; AD-D: Alzheimer's disease dementia; MCI: mild cognitive impairment.

Model inputs

Clinical parameter

The patient characteristics for the analysis were based on the information derived from hospital claims data provided by Medical Data Vision Co., Ltd to reflect actual clinical practice in Japan.¹⁸ The average age of the 116 patients who received lecanemab by June 2024 was 71.46 years (standard deviation: 8.3) and 68% of the patients were female.

AD severity was defined based on CDR-SB, measured by Clarity AD, with CDR-SB of 0.5–4.0 defined as MCI due to AD, 4.5–9.0 as Mild AD-D, 9.5–15.5 as Moderate AD-D, and 16.0–18.0 as Severe AD-D, respectively.¹⁹ Transition probabilities during months zero to 18 of the Markov model were obtained directly from Clarity AD and calculated from the baseline and month 18 distributions of patients across each health state.⁷

After 18 months, the relative efficacy of lecanemab was adapted as a reduced probability of transitioning to a worse health state, by way of a hazard ratio (HR). The HR of lecanemab to SOC was 0.704, calculated using 36-month data from Clarity AD, including an OLE study, and matching cohort data.^20,21 The same HR was applied to forward transitions from MCI due to AD and mild AD-D health states. Because the OLE study is a single-arm trial (non-comparative study), the Alzheimer's Disease Neuroimaging Initiative (ADNI)-matched cohort that matched the baseline patient background of the lecanemab arm in the Clarity AD was used as an external control.

The ADNI Study was used to design Study 301, selecting a priori a representative early AD observational cohort from ADNI (ADNI natural history cohort) and then using this longitudinal data to calculate natural/placebo decline over an 18-month period.

The observational cohort criteria matched the planned key inclusion criteria and study population for Study 301: (1) baseline diagnosis of “MCI” with global CDR = 0.5 and CDR memory ≥0.5 or baseline diagnosis of “AD” with global CDR = 0.5 or 1.0 and CDR memory ≥0.5, (2) proportion of MCI (60%) and mild AD (40%), (3) baseline Mini-Mental State Examination (MMSE) ≥ 22,(4) at least 1 of 2 criteria for amyloid positivity, (4a) baseline amyloid positron emission tomography (PET) SUVr florbetapir ≥1.11 or amyloid PET SUVr Pittsburgh compound B (PIB) ≥ 1.47 or (4b) baseline cerebrospinal fluid (CSF) total tau/Aβ>0.222.

In this analysis, propensity score matching was not conducted. Instead, patients in the ADNI cohort who met the specified criteria were selected and directly used as the control group for comparison with LEC, Standardized mean difference (SMD) between Study 301 and ADNI matched cohort was calculated in Table 2.²² Some variables show SMD > 0.1., but the ADNI natural history cohort was considered a representative matched control for efficacy analyses as 1) cohort is selected using key factors, 2) mixed model for repeated measures includes the planned factors same as primary analysis in Study 301, and 3) the adjusted mean change from baseline by 18 months are overlapped between Study 301 Placebo group and ADNI. The detail information on the ADNI methodology was provided in the following supplemental material of the cited article.²²

Table 2.

Demographic and baseline characteristics between study 301 and ADNI for overall population.

Overall population	Study 301 combined total randomized set	ADNI	Standardized mean difference (Combined total versus ADNI)
N	1795	436
Age
Mean (SD)	71.3 (7.83)	73.8 (7.38)	−0.33
Median	72.0	74.4
APOE4 Carrier Status
Positive n (%)	1231 (68.6%)	305 (70.0%)	−0.03
Negative n (%)	564 (31.4%)	131 (30.0%)
Disease Stage, n (%)
MCI due to AD	1107 (61.7%)	267 (61.2%)	0.01
Mild AD	688 (38.3%)	169 (38.8%)
Baseline CDR-SB
Mean (SD)	3.20 (1.340)	2.66 (1.662)	0.35
Median	3.00	2.50

AD: Alzheimer's disease; ADNI: Alzheimer's Disease Neuroimaging Initiative; APOE4: apolipoprotein E4; CDR-SB: Clinical Dementia Rating—Sum of Boxes; MCI: mild cognitive impairment; SD: standard deviation.

Regarding treatment continuity, approximately 96% of subjects completed treatment during the RCT phase of Clarity AD, and about 96.1% of those who completed treatment in the lecanemab arm transitioned to the OLE study. Since the continuation rates of lecanemab administration in the RCT and OLE studies hardly changed, it was assumed that the data from the latter do not significantly differ from those of the former in the RCT.

The estimation of this HR included data after treatment discontinuation and used mixed-effects models for repeated measures (MMRM) to account for dropout, so it was assumed that the HR for progression inhibition also applied to cases of lecanemab treatment discontinuation. When lecanemab administration was discontinued due to transition to moderate AD-D, the HR was assumed to be one, without considering further improvement.

Natural history data on AD progression after 18 months on SOC were derived from Potashman et al., who reported progression rates for the Aβ-positive cohort based on the National Alzheimer's Coordinating Center Uniform Data set, a large number of patients from a real-world population in the United States (US).²³ The model included backward transitions (i.e., to milder health states), as reported in Clarity AD, and identified natural history reports.⁷ However, since AD is an irreversible disease, these improvements may only be temporary and were assumed to occur solely in the first five years of the analysis and at the same rate in both treatments beyond 18 months. The analysis considered the increased mortality due to AD. The relative effects of mortality, as reported by Takata et al., who examined the relationship between cognitive function and mortality in Japanese patients with AD, were applied to the general Japanese population life tables.^24,25

The risk of institutionalization by health state is informed by published natural history data.²⁶ Patients were assumed to transition to institutional health states at a constant rate within each health state, and transitions from institutional to community health states were not considered.

Discontinuation of lecanemab was estimated based on 36-month data from Clarity AD.⁸ The rate of all-cause discontinuation of lecanemab followed that of the study treatment in Clarity AD for up to 36 months and a constant rate was set thereafter because the latter was relatively constant in Clarity AD.

All clinical parameters are shown in Supplemental Table 1.

Patient utilities

Patient utilities for each health state according to AD severity were estimated by Ashizawa et al. A health economic analysis, citing Ashizawa et al.,²⁷ reported utilities by AD severity for Japanese AD patients in institutions, as assessed by caregivers using the EQ-5D-5L. Since the utilities reported by Ashizawa et al. were for patients with institutionalized AD, the analysis used differences in utilities between MCI and mild to severe AD-D. The utility for patients with MCI due to AD was assumed to be the norm for the Japanese population in their 70 s,²⁸ and the utilities from mild to severe AD-D were calculated by applying the differences in utilities between MCI and mild-to-severe AD-D to the population norm.

The transition from community to institutional care is often associated with reduced QOL of patients; therefore, the analysis considered a decrease in QOL due to institutionalization. The decline in utility due to institutionalization was derived from a study by Farina et al., who compared the differences in EQ-5D utility scores between community and institutional care.²⁹ The coefficient for the impact of living in a care home on patients by proxy-reported EQ-5D was −0.13 (p = 0.01), while that for the impact of living in a care home on patient-reported EQ-5D was 0.00, which were not significantly different (p = 0.95). A previous study showed that patient-reported and caregiver-reported EQ-5D scores diverged significantly as disease severity increased.³⁰ Therefore, in the analysis, health-related QOL for the patient were assessed for subjects by proxy estimates in the moderate and severe AD-D health states. Consequently, no utility decrement was applied to institutionalized patients in the MCI due to AD/mild AD-D health state, while a 0.13 decrement was applied to institutionalized patients in the moderate/severe AD-D health states.

The patient utilities are shown in Supplemental Table 2.

Caregiver utilities

Dementia imposes significant physical and mental burdens not only on the patients themselves, but also on their family caregivers, and it is known that the QOL of family caregivers also declines alongside that of the patients.^31,32

In the evaluation of lecanemab by the Institute for Clinical and Economic Review (ICER) in the US, the analysis from the “Modified Societal Perspective,” which considered the QOL of family caregivers, was treated as equivalent to the base case analysis along with the “Healthcare Sector perspective."³³

Additionally, the National Institute for Health and Care Excellence (NICE) in the UK states that it is necessary to consider all the health impacts on both, patients and family caregivers.³⁴

Guidelines from the Task Force on Spillovers in Health Economic Evaluation and Research (SHEER) recommend the inclusion of spillover effects for family caregivers, regardless of the analytical perspective.

Based on the above, this analysis considered the QOL of family caregivers from all analytical perspectives.

Although the caregiver utility decrement method, which subtracts the caregiver's utility loss from the patient's utility, is often used, it does not reflect the caregiver's utility decline when the patient dies. This leads to an evaluation that diminishes the true treatment value by suggesting that not prolonging life results in less utility loss for the caregiver.³⁵

Therefore, in this study, the combined method for patient and caregiver utilities, which is one of the approaches examined in Large's report that considered ways to incorporate caregiver QOL into cost-utility analyses, was used in the base case analysis.³⁶ This method models the caregiver's utility by summing the absolute values of utility for both the caregiver and patient in each cycle.

Additionally, to evaluate the impact of different methods of considering caregiver utility, scenario analyses were conducted, including those using the utility decrement and the utility increment methods. The latter, examined by Large et al., is an approach that adds the caregiver's utility increment, obtained by the patient maintaining their health condition, to the patient's utilities.

The caregiver utilities for the mild to severe AD-D health states were taken from a study by Black et al.,³⁷ who reported EQ-5D-3L decrements from a regression analysis based on data from a large cross-sectional survey of physicians, consulting patients, and caregivers in France, Germany, Italy, Spain, the UK, and the US. The utility decrements for caregivers were 0.018, 0.033, and 0.020 for patients with mild, moderate, and severe AD-D, respectively. The utility for the caregivers of patients with MCI due to AD was assumed to be the norm for the Japanese population in their 60 s,²⁸ and the utilities for the caregivers of patients with mild to severe AD-D were calculated by applying the utility decrement of Black et al. to the utilities for the caregivers of patients with MCI due to AD to assess caregiver utility. A further utility decrement of 0.05 was assumed once a patient had been institutionalized because the study by Farina et al. showed that the caregivers of patients in long-term care settings were more likely to experience a decline in QOL.²⁹ Caregiver utility scores are shown in Supplemental Table 3. Furthermore, a scenario analysis was conducted excluding caregiver utility to calculate patient-only QALYs.

Costs

The lecanemab regimen consisted of a 10 mg/kg intravenous infusion every two weeks. The mean patient weight was set at 50 kg according to the Japanese drug pricing rule, and the mean compliance rate of 94.18% (standard deviation: 10.2) in the lecanemab arm in Clarity AD was used for compliance with lecanemab treatment. Before commencing lecanemab treatment, 47% of the patients were diagnosed using PET and 53%, using CSF tests, based on the payment data provided by Medical Data Vision Co., Ltd

Further, the monitoring costs of lecanemab were set in accordance with the guidelines for promoting optimal use.³⁸ Costs for magnetic resonance imaging scans at two, three, and six months after the beginning of administration and every six months or later, as well as those for assessments using the CDR or MMSE every six months, were calculated as monitoring expenses.

Medical and long-term care costs according to AD severity were calculated using reported values derived from the LIFE Study database at Kyushu University.³⁹ In Japan, medical expenses and long-term care expenses are covered by national insurance system and the long-term care insurance system, respectively. Medical services are covered by national insurance system, while expenses for long-term care in facilities or home-based care are covered by long-term care insurance. In the LIFE Study, medical care, long-term care, health checkups, and administrative data were collected at the municipal level, and a database integrating each type of data was constructed.

Based on data from April 2021 to March 2022 aggregated for patients with a history of AD diagnosis as of April 2021, medical and long-term care costs were estimated by severity.

In this study, a scenario analysis from a societal perspective was conducted, considering informal care costs of caregivers in addition to the costs considered in the base-case analysis. Informal costs of caregivers (by disease-severity) in community care locations were obtained from previous study, while no informal costs in the institutional care settings were considered in the analysis.⁹

All cost parameters are listed in Supplemental Table 4 and key resource-use and modeling setting are summarized in Supplemental Table 5.

Analysis

The analysis was performed separately for each clinical subpopulation of MCI due to AD and mild AD-D, as defined by the CDR-SB at baseline, to assess the impact of the baseline condition on the cost-effectiveness of lecanemab. The QALYs and ICERs were calculated to assess the cost-effectiveness of lecanemab compared with SOC. The time spent in each severity level of AD was also calculated, and the progression of AD per treatment was evaluated. Additionally, this analysis estimated the benchmark price of lecanemab at willingness-to-pay (WTP) thresholds of JPY 5 million (USD 33,333), JPY 7.5 million (USD 50,000), JPY 10 million (USD 66,667), and JPY 15 million (USD 100,000) to evaluate costs based on the value of lecanemab. The benchmark price was defined as the annual drug cost at which the ICER equals each WTP threshold. The annual cost of lecanemab was calculated based on the assumption of using 26 vials of 500 mg per year.

Sensitivity analysis

To account for the uncertainty around the model parameters and test the robustness of the model, the deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed. The DSA model inputs varied by 95% when confidence intervals (CIs) were available, and by ± 20% of the base-case value when CIs were not publicly available. The distribution parameters of PSA were all set based on the standard error of the base-case values; however, for parameters where the standard error was not reported or could not be estimated, it was calculated from the upper and lower limits of the 95% CI assumed to be ±20% of the set values and then set accordingly. The PSA followed a standard Monte Carlo approach consisting of 10,000 randomly drawn simulations of the parameter values. The setting ranges and distributions of each variable are listed in Supplemental Tables 1–4.

Table 3.

Base-case results.

	MCI due to AD population			Mild AD population
	SoC	LEC + SoC	Δ*	SoC	LEC + SoC	Δ*
Total LYS (discounted)	9.21	9.81	0.61	8.42	8.80	0.38
Total QALYs (discounted)	14.05	15.36	1.31	12.15	13.00	0.85
Patient QALYs	6.21	6.96	0.75	5.10	5.59	0.49
Caregiver QALYs	7.84	8.40	0.56	7.06	7.42	0.36
Time on treatment (undiscounted, years)	−	4.18	−	−	2.41	−
Total costs (JPY, discounted))	15,386,703	26,462,950	11,076,246	18,904,147	25,556,866	6,652,719
Total medical costs	5,520,520	17,768,733	12,248,213	6,501,738	13,860,998	7,359,260
Lecanemab drug cost	0	12,113,548	12,113,548	0	7,157,157	7,157,157
Administration costs	0	187,449	187,449	0	110,752	110,752
Monitoring costs	0	183,795	183,795	0	130,221	130,221
Screening costs	0	117,928	117,928	0	117,928	117,928
Symptomatic treatment costs	52,737	47,086	−5651	70,666	69,057	−1610
Direct medical costs	5,466,298	5,114,354	−351,944	6,429,587	6,271,311	−158,276
AE costs	1485	4573	3087	1485	4573	3087
Long-term care costs	9,866,183	8,694,217	−1,171,966	12,402,408	11,695,868	−706,541
ICER (JPY per QALY)	−	−	8,456,482	−	−	7,858,671
Benchmark price of lecanemab (JPY/year)
WTP threshold of
JPY 5 million	−	−	1,863,420	−	−	1,969,370
JPY 7.5 million	−	−	2,667,730	−	−	2,849,288
JPY 10 million	−	−	3,472,118	−	−	3,729,128
JPY 15 million	−	−	5,080,738	−	−	5,488,808

* Δ represents the incremental difference between LEC + SoC and SoC alone.

AD: Alzheimer's disease; ICER: incremental cost-effectiveness ratio; LEC: lecanemab; LYS, life years; MCI: mild cognitive impairment; QALY: quality adjusted life year; SoC: standard of care; WTP: willingness to pay.

Table 4.

Results of scenario analysis (MCI due to ad population).

	Treatment	Total costs (JPY)	Δ^*1	Total QALYs	Δ^*1	ICER (JPY/QALY)	Benchmark price of lecanemab (JPY/year)
							WTP threshold of
							JPY 5 million	JPY 7.5 million	JPY 10 million	JPY 15 million
Base-case	LEC	26,462,950	11,076,246	15.36	1.31	8,456,482	1,863,420	2,667,730	3,472,118	5,080,738
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
Scenario analysis: Perspective
public healthcare payer	LEC	17,768,733	12,248,213	15.36	1.31	9,351,254	1,575,548	2,379,858	3,184,220	4,792,840
	SoC	5,520,520	−	14.05	−	−	−	−	−	−
societal	LEC	40,947,778	10,054,273	15.36	1.31	7,676,227	2,114,450	2,918,760	3,723,148	5,331,768
	SoC	30,893,505	−	14.05	−	−	−	−	−	−
Scenario analysis: Caregiver utility approach
decrement method	LEC	26,462,950	11,076,246	6.65	0.80	13,813,361	1,239,550	1,731,990	2,224,378	3,209,180
	SoC	15,386,703	−	5.85	−	−	−	−	−	−
increment method	LEC	26,462,950	11,076,246	7.84	0.88	12,653,172	1,329,900	1,867,450	2,405,000	3,480,100
	SoC	15,386,703	−	6.96	−	−	−	−	−	−
excluding	LEC	26,462,950	11,076,246	6.96	0.75	14,829,815	1,172,080	1,630,720	2,089,360	3,006,718
(patient utility only)	SoC	15,386,703	−	6.21	−	−	−	−	−	−
Scenario analysis: Treatment effect waning ^*2
no waning	LEC	23,492,862	8,106,159	15.38	1.33	6,112,431	2,500,550	3,567,850	4,635,228	6,769,828
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
waning over 12.0 years	LEC	23,608,868	8,222,164	15.21	1.16	7,078,072	2,198,378	3,133,260	4,068,168	5,937,958
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
waning over 7.6 years	LEC	23,660,771	8,274,068	15.15	1.09	7,558,214	2,073,890	2,954,978	3,835,988	5,598,060
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
waning over 2.6 years	LEC	23,790,243	8,403,540	15.00	0.95	8,853,160	1,798,030	2,561,988	3,325,920	4,853,810
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
Scenario analysis: Relative efficacy for lecanemab
HR: 0.729	LEC	26,433,779	11,047,076	15.25	1.20	9,204,595	1,721,720	2,467,218	3,212,638	4,703,530
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
HR: 0.679	LEC	26,492,151	11,105,448	15.48	1.42	7,796,907	2,008,240	2,872,818	3,737,370	5,466,500
	SoC	15,386,703	−	14.05	−	−	−	−	−	−
Scenario analysis: Starting age
65 years	LEC	34,019,045	10,824,612	18.71	1.41	7,689,402	2,079,168	2,912,338	3,745,560	5,411,978
	SoC	23,194,433	−	17.30	−	−	−	−	−	−
75 years	LEC	22,791,592	11,012,880	13.49	1.20	9,170,456	1,701,518	2,465,190	3,228,888	4,756,258
	SoC	11,778,711	−	12.29	−	−	−	−	−	−
Scenario analysis: Maintenance dose
Administration every 4 weeks after 18 months	LEC	22,429,150	7,042,446	15.36	1.31	5,376,761	2,795,130	3,991,910	5,188,690	7,582,250
Administration every 4 weeks after 18 months	SoC	15,386,703	−	14.05	−	−	−	−	−	−
Scenario analysis: Drug price^*3
HTA-adjusted drug price	LEC	24,645,871	9,259,168	15.36	1.31	7,069,181	1,863,420	2,667,730	3,472,118	5,080,738
	SoC	15,386,703	−	14.05	−	−	−	−	−	−

*1 Δ represents the incremental difference between LEC + SoC and SoC alone *2 Assuming treatment discontinuation at 5 years after initiation, followed by a linear disappearance of the treatment effect.* 3 Reflecting the revised drug price based on the results of the Health Technology Assessment (JPY 38,910 for 200 mg and JPY 97,277 for 500 mg).

AD: Alzheimer's disease; HR: hazard ratio; HTA: health technology assessment; ICER: incremental cost-effectiveness ratio; LEC: lecanemab; MCI: mild cognitive impairment; QALY: quality adjusted life year; SoC: standard of care; WTP: willingness to pay.

Scenario analysis

Scenario analyses were conducted under various assumptions as follows.

First, scenarios were conducted from different perspectives: the public healthcare payer perspective and the societal perspective.

Second, regarding the inclusion of caregiver utility, three alternative scenarios (decrement method, increment method, and excluding caregiver utility) were examined to test the impact of different utility accounting approaches.

Third, to account for the uncertainty regarding the long-term persistence of the treatment effect, waning scenarios were conducted. Based on the OLE study data confirming efficacy up to 48 months, we assumed treatment discontinuation at 5 years after treatment initiation, and examined three scenarios: (i) no waning of the treatment effect, and a linear disappearance of the treatment effect (HR) to 1.0 (no effect) over subsequent periods of (ii) 12.0 years, (iii) 7.6 years, and (iv) 2.6 years. In these scenarios, a gradual loss of treatment effect begins immediately post-treatment stop, with subsequent linear waning from a full treatment effect down to the rate of placebo / natural decline over the course of 2.6 years, 7.6 years and 12.0 years. This waning effect for 2.6 years is the estimated time for the average patient in Clarity AD to reaccumulate amyloid PET levels back to 30 CL (based on exponential re-accumulation). This 30 CL threshold indicates the presence of established AD pathology, including p-tau, t-tau, and their ratio with Aβ₄₂, and represents a conservative threshold above which there is a high certainty that a relevant amount of amyloid pathology is established.⁴⁰ The wider published literature also suggests that patients with amyloid PET levels below 50 CL show little to no clinical progression within the subsequent 3.4 to 4.5 years, across three different studies.^41–43 It is estimated to take approximately 7.6 years for the average patient's amyloid PET levels to reaccumulate above 50 CL post-treatment stop. Furthermore, a 12.0-year scenario represents the estimated time for amyloid PET to return to the Clarity AD study baseline levels.

Fourth, scenario analyses were conducted wherein the HR for the relative efficacy of lecanemab varied. In the base case analysis, the HR was estimated based on 36 months of data from Clarity AD; however, analyses were also conducted using HRs estimated from 18- and 48-month data from Clarity AD, yielding values of 0.729 (95% CI: 0.604–0.881) and 0.679 (95% CI: 0.575–0.802), respectively.

Fifth, we examined the impact of different ages of onset (65 and 75 years) for the target population.

Sixth, an analysis was conducted assuming the introduction of a maintenance dose—already approved in the United States—changing the dosing frequency from every two weeks to every four weeks after 18 months.

Finally, a scenario was performed using the HTA-adjusted drug price in Japan (JPY 38,910 for 200 mg and JPY 97,277 for 500 mg), implemented in November 2025 to reflect the revised price following the official cost-effectiveness evaluation process.⁴⁴

Results

Base-case analysis

The estimated mean duration of treatment with lecanemab was 4.18 years in the “MCI due to AD” population and 2.41 years in the “mild AD-D” population. The analysis estimated a slower rate of disease progression for lecanemab + SOC than for SOC alone in both target populations. In the MCI due to AD population, treatment with lecanemab delayed the onset of dementia, and patients treated with lecanemab spent a further 1.63 years in early AD and 0.85 years less in moderate and severe AD-D than patients treated with SOC alone. In the mild AD-D population, patients treated with lecanemab spent a further 1.08 years in early AD and 0.61 years less in moderate and severe AD-D. Figure 2(a) and (b) exhibits the average length of stay according to AD severity in patients used in the base-case analysis.

Figure 2.

(a) Patient disposition in different AD severity levels or death over lifetime. (b) Mean patient life years and QALYs. AD: Alzheimer's disease; AD-D: Alzheimer's disease dementia; LEC: lecanemab; MCI: mild cognitive impairment; SOC: standard of care.

Additionally, lecanemab + SOC delayed disease progression, thereby extending both, the time to institutionalization and of overall survival.

Compared to SOC, lecanemab + SOC prolonged the time spent in community settings by 0.97 years in the MCI due to AD population and by 0.56 years in the mild AD-D population, and extended survival by 0.78 years in the former and by 0.48 years in latter, respectively.

The lifetime QALYs gained by patients in the MCI due to AD and mild AD-D populations were 6.21 and 5.10 for SOC, and 6.96 and 5.59 for lecanemab + SOC, with the incremental effect of lecanemab + SOC being 0.75 QALYs and 0.49 QALYs. The incremental QALYs of lecanemab + SOC on caregivers’ QALYs were 0.56 in the MCI due to AD population and 0.36 in the mild AD-D population.

In the MCI due to AD population, the total cost for the lecanemab increased by JPY 11,076,246 (USD 73,842) compared to that for the SOC. The breakdown is as follows: costs related to lecanemab, including those for drugs, administration, diagnostic tests, and monitoring, increased by JPY 12,113,548 (USD 80,757), medical expenses decreased by JPY 351,944 (USD 2346), and long-term care costs decreased by JPY 1,171,966 (USD 7813) due to lecanemab treatment.

In the mild AD-D population, the total cost for the lecanemab increased by JPY 6,652,719 (USD 44,351) compared to that for the SOC. The breakdown showed an increase in lecanemab-related costs by JPY 7,157,157 (USD 47,714), but medical expenses and long-term care costs were reduced by JPY 158,276 (USD 1055) and JPY 706,541 (USD 4710), respectively, owing to lecanemab treatment.

From the perspective of public healthcare and long-term care payers, the ICER for lecanemab + SOC was JPY 8,456,482 (USD 56,377) per QALY for the MCI population and JPY 7,858,671 (USD 52,391) per QALY for the mild AD-D population.

The estimated the benchmark price of lecanemab based on the WTP thresholds of JPY 5 million (USD 33,333), JPY 7.5 million (USD 50,000), JPY 10 million (USD 66,667), and JPY 15 million (USD 100,000) is as follows:

JPY 1,863,420 (USD 12,423)、JPY 2,667,730 (USD 17,785)、JPY 3,472,118 (USD 23,148)、JPY 5,080,738 (USD 33,872), for the MCI due to AD population, respectively, and JPY 1,969,370 (USD 13,129), JPY 2,849,288 (USD 18,995), JPY 3,729,128 (USD 24,861), and JPY 5,488,808 (USD 36,592) for the mild AD-D population, respectively. The base case results are listed in Table 3.

Sensitivity analysis

Sensitivity analyses were conducted on the base-case analysis. In the DSA, the subsequent impact on cost-effectiveness can be assessed by varying one parameter at a time. The parameter with the greatest impact on ICER was the treatment effect of lecanemab after 18 months (time to worsening HR) in both target populations. Next, the discount rate and weight parameters demonstrated significant impacts. The ICER tornado diagrams for the top ten parameters with the greatest impact are shown in Figure 3.

Figure 3.

Deterministic sensitivity analysis results. AD: Alzheimer's disease; AD-D: Alzheimer's disease dementia; HR: hazard ratio; LEC: lecanemab; MCI: mild cognitive impairment.

In the PSA, 10,000 Monte Carlo simulations were recorded and plotted over time to demonstrate the ICER convergence. The incremental cost-effectiveness plane and acceptability curves are shown in figures 4 and 5, respectively. When the ICER thresholds of JPY 5 million (USD 33,333) /QALY, JPY 7.5 million (USD 50,000) /QALY, JPY 10 million (USD 66,667) /QALY and JPY 15 million (USD 100,000) /QALY were used, the probabilities of the cost-effectiveness of lecanemab were 1.2%, 30.8%, 73.1%, and 97.1% in the MCI due to AD population and 4.4%, 42.7%, 77.5%, and 96.6% in the mild AD-D population, respectively.

Figure 4.

Cost-effectiveness plane. AD: Alzheimer's disease; AD-D; Alzheimer's disease dementia; MCI: mild cognitive impairment; QALY: quality adjusted life year; SOC: standard of care.

Figure 5.

Cost-effectiveness acceptability curves (CEAC) of base-case analysis. AD: Alzheimer's disease; AD-D: Alzheimer's disease dementia; MCI: mild cognitive impairment; SOC: standard of care.

Scenario analysis

The results of all scenario analyses are presented in Tables 4 and 5.

Table 5.

Results of scenario analysis (Mild AD population).

	Treatment	Total costs(JPY)	Δ^*1	Total QALYs	Δ^*1	ICER(JPY/QALY)	Benchmark price of lecanemab (JPY/year)
							WTP threshold of
							JPY 5 million	JPY 7.5 million	JPY 10 million	JPY 15 million
Base-case	LEC	25,556,866	6,652,719	13.00	0.85	7,858,671	1,969,370	2,849,288	3,729,128	5,488,808
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
Scenario analysis: Perspective
public healthcare payer	LEC	13,860,998	7,359,260	13.00	0.85	8,693,287	1,675,648	2,555,540	3,435,380	5,195,060
	SoC	6,501,738	−	12.15	−	−	−	−	−	−
societal	LEC	42,823,883	6,154,100	13.00	0.85	7,269,665	2,176,668	3,056,560	3,936,400	5,696,080
	SoC	36,669,784	−	12.15	−	−	−	−	−	−
Scenario analysis: Caregiver utility approach
decrement method	LEC	25,556,866	6,652,719	5.14	0.52	12,754,239	1,293,968	1,836,068	2,378,220	3,462,498
	SoC	18,904,147	−	4.62	−	−	−	−	−	−
increment method	LEC	25,556,866	6,652,719	6.21	0.57	11,712,102	1,390,428	1,980,810	2,571,140	3,751,930
	SoC	18,904,147	−	5.64	−	−	−	−	−	−
excluding	LEC	25,556,866	6,652,719	5.59	0.49	13,603,034	1,226,290	1,734,590	2,242,890	3,259,490
(patient utility only)	SoC	18,904,147	−	5.10	−	−	−	−	−	−
Scenario analysis: Treatment effect waning ^*2
no waning	LEC	24,810,040	5,905,893	13.01	0.85	6,925,525	2,216,448	3,201,978	4,187,430	6,158,490
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
waning over 12.0 years	LEC	24,847,491	5,943,344	12.95	0.79	7,508,318	2,057,640	2,972,450	3,887,208	5,716,828
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
waning over 7.6 years	LEC	24,864,689	5,960,542	12.92	0.77	7,784,797	1,989,858	2,874,690	3,759,548	5,529,238
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
waning over 2.6 years	LEC	24,911,000	6,006,853	12.86	0.70	8,545,326	1,823,458	2,635,828	3,448,198	5,072,938
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
Scenario analysis: Relative efficacy for lecanemab
HR: 0.729	LEC	25,539,536	6,635,389	12.93	0.78	8,505,677	1,827,098	2,646,020	3,464,968	5,102,838
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
HR: 0.679	LEC	25,574,446	6,670,299	13.07	0.92	7,277,191	2,116,530	3,059,498	4,002,518	5,888,428
	SoC	18,904,147	−	12.15	−	−	−	−	−	−
Scenario analysis: Starting age
65 years	LEC	34,077,388	6,404,478	16. 30	0.87	7,371,677	2,138,968	3,020,758	3,902,548	5,666,050
	SoC	27,672,909	−	15.43	−	−	−	−	−	−
75 years	LEC	21,473,713	6,704,734	11.22	0.80	8,365,020	1,828,138	2,680,548	3,532,958	5,237,700
	SoC	14,768,980	−	10.42	−	−	−	−	−	−
Scenario analysis: Maintenance dose
Administration every 4 weeks after 18 months	LEC	23,758,703	4,854,556	13.00	0.85	5,734,551	2,631,980	3,801,070	4,970,160	7,308,418
Administration every 4 weeks after 18 months	SoC	18,904,147	−	12.15	−	−	−	−	−	−
Scenario analysis: Drug price^*3
HTA-adjusted drug price	LEC	24,483,265	5,579,118	13.00	0.85	6,590,456	1,969,370	2,849,288	3,729,128	5,488,808
	SoC	18,904,147	−	12.15	−	−	−	−	−	−

*1 Δ represents the incremental difference between LEC + SoC and SoC alone *2 Assuming treatment discontinuation at 5 years after initiation, followed by a linear disappearance of the treatment effect. * 3 Reflecting the revised drug price based on the results of the Health Technology Assessment (JPY 38,910 for 200 mg and JPY 97,277 for 500 mg).

AD: Alzheimer's disease; HR: hazard ratio; HTA: health technology assessment; ICER: incremental cost-effectiveness ratio; LEC: lecanemab; QALY: quality adjusted life year; SoC: standard of care; WTP: willingness to pay.

In the analysis from the public healthcare payer perspective, which excludes non-medical costs, the incremental cost was higher than the base case. This is because the long-term care cost-offsets were no longer captured, leading to a direct increase in the incremental cost. While, when analyzed from a societal perspective by considering informal care costs, the cost-effectiveness of lecanemab improved compared to the base-case analysis. This was due to a reduction in informal care costs: JPY 1,021,973 (USD 6813) for the MCI due to AD population [JPY 15.5 million (USD 103,379) versus JPY 14.5 million (USD 96,566)] and JPY 498,619 (USD 3324) for the mild AD-D population [JPY 17.8 million (USD 118,438) versus JPY 17.3 million (USD 115,113)]. Regarding caregiver utility, using the decrement or increment methods—or excluding caregiver utility—resulted in higher ICERs compared to the base case. The decrease in incremental effect was greater when the utility decrement method was used. The waning scenarios indicated that the ICERs fluctuated depending on the assumptions of treatment effect persistence. The scenario assuming that the treatment effect would persist even after treatment discontinuation at 5 years resulted in a more favorable ICER than the base-case due to the reduction in drug costs. Conversely, the scenarios assuming a stepwise disappearance of the treatment effect after discontinuation led to higher ICERs as the duration of effect persistence became shorter. In the scenario analysis, where the HR of lecanemab changed, the ICER fluctuated according to the treatment effect of lecanemab. In the scenario analysis where the starting age of the analysis was changed, the cost-effectiveness tended to improve in the younger population. Finally, both the introduction of a maintenance dose and the application of the HTA-adjusted drug price improved the cost-effectiveness, with the former bringing the ICER closer to JPY 5 million per QALY.

Discussion

This study assessed the social value and the benchmark price of lecanemab + SOC versus SOC in early AD using cost-effectiveness analysis. Clinical inputs came from Clarity AD and its subsequent OLE study, while Japanese data on costs, QOL, and epidemiology were incorporated to reflect real-world practice. Lecanemab was estimated to extend early AD stages, i.e., MCI due to AD and Mild AD, (1.63 years in MCI due to AD population, 1.08 years in mild AD population at the baseline) maintain higher health-related quality of life (HRQoL) and yield higher QALYs, and shorten moderate/severe stages (0.85 years in MCI, 0.61 in mild AD). Earlier intervention in MCI yielded greater benefits. This is considered to be because, by the time patients transition to the moderate or severe stages, they are older and therefore face a higher risk of death, resulting in a stronger influence of lifespan. Facility admission (institutionalization) and survival were also prolonged. Lecanemab + SOC extended time to facility admission and survival by 0.97 and 0.78 years in MCI, and 0.56 and 0.48 years in mild AD. These effects reflect epidemiological evidence that slowing disease progression reduces mortality risk.

Lecanemab increased QALYs for patients and caregivers by 0.85 QALY /0.64 QALY in MCI due to AD and 0.62 QALY /0.45 QALY in Mild AD. ICERs for lecanemab + SOC versus SOC ranged from JPY 9.4 M /QALY to JPY 7.3 M/QALY across perspectives, with higher ICERs in MCI due to AD despite greater health benefits, i.e., QALY. AD imposes growing caregiver burden beyond medical costs. Lecanemab may reduce this by slowing disease progression. Thus, analyses should include public long-term care and informal care costs, using both payer and societal perspectives. Although MCI due to AD patients gain more benefits, their ICER is higher due to longer treatment and higher drug costs, despite reduced care costs. This should not discourage early treatment; future maintenance dosing may improve cost-effectiveness.

In this study, PSA and DSA were conducted from a societal perspective to assess the uncertainty of the analytical results. The average value of the probabilistic ICER matched that of the deterministic ICER, demonstrating the robustness of the analysis results, even when considering parameter uncertainty. The results of the DSA revealed that the parameter that impacted cost-effectiveness most significantly was the treatment effect of lecanemab after 18 months, followed by the discount rate of health outcomes and body weight. AD is a progressive condition, and since the treatment effect of lecanemab after 18 months and the discount rate of health outcomes were applied over a long analysis period, the uncertainty of the results was high. Additionally, body weight affects the dosage of lecanemab, causing fluctuations in drug cost; since the varied drug cost was applied over a long period, its impact is believed to have been significant.

The previous study evaluating the societal value and the benchmark price of lecanemab was conducted prior to its approval and launch in Japan.⁹ Therefore, it could not reflect the actual post-marketing healthcare setting, for example the actual age and gender distribution of patients receiving treatment, the types of diagnostic methods used (PET/CSF), the indications, the content of the optimal use promotion guidelines and the conditions for providing medical institutions. Unanticipated aspects in the previous study were addressed by aligning with the clinical trial design or making assumptions. Regarding the efficacy of lecanemab, sustained effects were assumed due to the lack of long-term data. This study had data available up to 36 months after lecanemab administration. These data enabled the estimation of long-term effects by comparison with an ADNI cohort that was pre-selected a priori to match the clinical trial population. In previous studies, the analytical model was validated using disease progression data from the lecanemab phase 2 trial. This study verified internal, cross-, and external validity based on ISPOR's model validation recommendations.⁴⁵ Furthermore, in terms of face validity, the long-term disease progression estimated in our model aligned well with the natural history of AD in the Japanese population. Specifically, our model's output (Figure 2(a)) showed that approximately 50% of patients with MCI progressed to AD-D within 2 to 3 years. This is highly consistent with the findings from the J-ADNI study,⁴⁶ which reported a 50% conversion rate from MCI to AD-D over a similar duration. This consistency confirms that our model accurately reflects the clinical course of early AD in Japan.

This study had several limitations. First, the cost data for AD treatment and long-term care expenses may not reflect the actual situation in Japan. The available data linking long-term care costs and medical expenses are limited in Japan. Therefore, we used the results of the LIFE Study, which comprises data from multiple municipalities, as the best available data. Regarding the appropriateness of this cost, we used national cost statistics by level of long-term care needed across Japan, including non-AD patients, as well as a report on the distribution of long-term care levels to estimate costs by severity of AD. We confirmed that these estimates do not differ significantly from the long-term care costs observed in the LIFE Study and, therefore, consider this set value to exhibit a certain degree of validity. Second, patient utility values were sourced from prior Japanese studies, whereas caregiver utility values were derived from international literature. No reports have specified utility values for Japanese patients with MCI due to AD, confirmed to have Aβ accumulation, leading us to assume that the utility values for the general population in the target age group are applicable to patients with MCI due to AD. Third, regarding the efficacy after discontinuing lecanemab, because the estimation of this HR includes data after discontinuation and the estimation accounts for dropouts using the MMRM method, it is assumed that the HR for progression suppression also applies to cases wherein lecanemab administration was stopped. As there are no clinical trial data on the efficacy in patients after discontinuation, it is hoped that some data will be reported in real-world clinical practice in the future. This analysis, considering the indications for regulatory approval, assumed that the efficacy of lecanemab would immediately disappear and the hazard ratio would become one upon progression to moderate AD. However, because some patients with Moderate AD-D were included among those who continued treatment during the Clarity AD core period and at 48 months in the OLE period, this assumption is considered to be conservative. Finally, in Japan, the results of cost-effectiveness evaluations are used for drug price adjustments; when the ICER exceeds 5 million yen/QALY, the price may be gradually adjusted to 10 million yen/QALY. Assuming a benchmark value of 5 million yen per QALY, the estimated ICER of lecanemab treatment exceeds it in all analyses; however, considering that experts in the field recommend a WTP threshold five times higher for severe AD due to its debilitating nature and significant societal costs,⁴⁷ if this benchmark is hypothetically applied as the ICER standard value in Japan's HTA, the WTP threshold for AD would be 5 times (i.e., 25 million yen per QALY) or more, at least, there is a range according with the disease severity,⁴⁸ indicating that lecanemab is an acceptable treatment in all analyses. We also estimated benchmark prices based on WTP thresholds, calculated at WTP thresholds of 5 million yen, 7.5 million yen, 10 million yen, and 15 million yen, following the report by Igarashi et al., who evaluated the cost-effectiveness of lecanemab in Japan. As of December 2024, the drug price of Lecanemab (Leqembi^®) 500 mg in Japan is JPY 114,443. However, from the societal perspective, the benchmark price was estimated to be higher than the current price of lecanemab at a WTP threshold of 7.5 million yen per QALY or more. Even from the public healthcare payer perspective, the benchmark price was estimated to be higher than the current price at a WTP threshold of 10 million yen per QALY or more. Considering that the WTP for AD was higher than for other diseases,⁴⁷ the current price of lecanemab was considered appropriate in terms of benchmark price.

This was the first official attempt to expand the analytical perspective within HTA in Japan, however, consequently, the most conservative analysis from the “Public healthcare payer's perspective” was adopted for price adjustment. The reason why the “Public healthcare and long-term care payer's perspective” was not approved was that there were no data on long-term care costs linked with the disease severity information of AD, and it could only be estimated. Furthermore, the caregiver QOL was not included in the analysis because there is currently no academically established consensus on how to utilize it.

Conclusion

This study evaluated the social value and the benchmark price of lecanemab plus SOC in early AD patients, compared to SOC alone. Treatment with lecanemab has been suggested to benefit patients with AD and caregivers, compared with only SOC, by prolonging the duration of early AD and shortening the period of moderate and severe stages, thereby reducing mortality, maintaining HRQoL, lowering caregiver burden, and reducing the use of medical and long-term care resources. Considering the disease burden of AD, the current price of lecanemab reflects its social value in the Japanese healthcare system. Furthermore, when introducing a maintenance dose of lecanemab, the ICER approaches the price adjustment threshold of JPY5 million per QALY in Japan.

Supplemental Material

sj-docx-1-alz-10.1177_13872877261447312 - Supplemental material for The social value of lecanemab for patients with early Alzheimer's disease in Japan

Supplemental material, sj-docx-1-alz-10.1177_13872877261447312 for The social value of lecanemab for patients with early Alzheimer's disease in Japan by Ataru Igarashi, Mie Azuma-Kasai, Mayaka Tani, Takuro Utsumi, Hidetoshi Shibahara, Sachie Inoue, Simon Rothwell, Gaku Kamanaka, Yukinori Sakata, Hironobu Hiyoshi and Kiyoyuki Tomita in Journal of Alzheimer's Disease

Footnotes

Acknowledgements

The authors have no acknowledgments to report.

ORCID iDs

Ataru Igarashi

Mie Azuma-Kasai

Hidetoshi Shibahara

Ethical considerations

This analysis is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Consent to participate

Not applicable

Author contribution(s)

Ataru Igarashi: Conceptualization; Methodology; Writing – review & editing.

Mayaka Tani: Conceptualization; Writing – review & editing.

Mie Kasai Azuma: Conceptualization; Methodology; Writing – review & editing.

Takuro Utsumi: Conceptualization; Writing – review & editing.

Hidetoshi Shibahara: Methodology; Writing – original draft; Writing – review & editing.

Sachie Inoue: Methodology; Writing – review & editing.

Simon Rothwell: Methodology; Writing – review & editing.

Gaku Kamanaka: Conceptualization; Writing – review & editing.

Yukinori Sakata: Conceptualization; Writing – review & editing.

Hironobu Hiyoshi: Conceptualization; Writing – review & editing.

Kiyoyuki Tomita: Conceptualization; Writing – review & editing.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study has been funded by Eisai Co. Ltd., Japan. The funder contributed to the study design, and provided comments on drafts of the manuscript. All authors were responsible for the data analysis and interpretation. The final decision to submit the paper for publication was made by the authors.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ataru Igarashi received consultant fee from Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd, Eli Lilly Japan K.K. and Novo Nordisk Pharma Ltd. Mie Azuma-Kasai, Mayaka Tani, Takuro Utsumi, Gaku Kamanaka, Yukinori Sakata, Hironobu Hiyoshi, Kiyoyuki Tomita and Simon Rothwell are employes of Eisai Co., Ltd. Hidetoshi Shibahara, and Sachie Inoue are current employes of CRECON Medical Assessment inc., a healthcare research firm. Eisai Co., Ltd. provided funding to CRECON Medical Assessment inc. for conducting the analysis and preparing the manuscript.

Data availability statement

The data supporting the findings of this study are available within the article and/or its Supplemental Material. Additional details are available from the corresponding author upon request.

Supplemental material

Supplemental material for this article is available online.

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