Estimated Societal Value of Lecanemab in Patients with Early Alzheimer’s Disease Using Simulation Modeling

Abstract

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory, cognitive, and behavioral deficits, and brings significant economic burden on caregivers and healthcare systems. This study aims to estimate the long-term societal value of lecanemab plus standard of care (SoC) versus SoC alone, corresponding to a range of willingness-to-pay (WTP) thresholds based on the phase III CLARITY AD trial readouts from both the US payer and societal perspectives. Methods: An evidence-based model was developed to simulate the effects of lecanemab on disease progression in early AD using interconnected predictive equations based on longitudinal clinical and biomarker data derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The model was informed with the results of the phase III CLARITY AD trial and published literature. Key model outcomes included patient life-years (LYs), quality-adjusted life-years (QALYs), and total costs of both the direct and indirect costs of patients and caregivers over a lifetime horizon. Results: Patients treated with lecanemab plus SoC gained an additional 0.62 years of life versus SoC alone (6.23 years vs. 5.61 years). The mean time on lecanemab was 3.91 years, and the treatment was associated with an increase in patient QALYs of 0.61 and an increase in total QALYs of 0.64 when both patient and caregiver utilities were considered. The model estimated that the annual value of lecanemab for the US payer perspective was US$18,678 ($19,351 for societal perspective) at the WTP threshold of $100,000-200,000 per QALY gained, respectively. Scenario analyses of patient subgroups, time horizon, input sources, treatment stopping rules, and treatment dosing were conducted to explore the impact of alternative assumptions on the model results. Conclusion:The economic study suggested that lecanemab plus SoC would improve health and humanistic (quality of life) outcomes and reduce economic burden for patients and caregivers in early AD.

New IPECAD open-source model framework for the health technology assessment of early Alzheimer’s disease treatment: development and use cases

“…Whittington et al (40) showed a lower incremental cost-effectiveness ratio with aducanumab treatment stopping at an earlier severity state and diminished outcomes with stronger treatment effect waning assumptions. AD-ACE model applications (22,34,41) showed higher lecanemab treatment value with higher discontinuation rates, with maintained reduced amyloid level after stopping treatment and with lower dosing frequency while assuming no treatment effect waning, and lower lecanemab treatment value with shorter maximum treatment duration. Kongpakwattana et al (42) showed a higher cost-effectiveness ratio with earlier stopping donepezil at severe dementia.…”

“…The second use case is the cross-validation of a model published by Tahami Monfared et al (22) which was funded by Eisai, the sponsor of the lecanemab phase 3 trial. They used the Alzheimer's Disease ACE Simulator (AD-ACE) model (32) which uses a patient-level microsimulation approach capturing domains for AD pathology (e.g., beta-amyloid biomarkers), cognition, function, behavior and dependency.…”

“…For the appraisal of current and possible future AD drugs, we argue that an open-source model with intuitive model structure that is easy to use for model cross-validation is urgently needed to support transparency and credibility of new AD drug cost-effectiveness assessments. Therefore, we describe the new IPECAD open-source model framework (version 2) for the health-economic evaluation of early AD treatment and aim to apply it in 3 use cases for AD lecanemab treatment: 1) cross-validating an existing model with a similar structure (ICER (21)), 2) cross-validating an existing model with a more complex structure (AD-ACE (22)) and 3) assessing additional uncertainty scenarios.…”