A Path to Improved Alzheimer's Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer's Disease from the CLARITY AD Trial

Abstract

Introduction: Alzheimer's disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and one of the leading causes of death for elderly people in the USA. Lecanemab is a humanized IgG1 monoclonal antibody targeting amyloid protofibrils for the treatment of early AD [i.e., mild cognitive impairment (MCI) or mild AD dementia]. In a recent 18-month phase III trial, using a double-blind, placebo-controlled design, lecanemab treatment led to reduced brain amyloid burden and significant improvements in cognitive and functional abilities in individuals with early AD.

Methods: An evidence-based patient-level disease simulation model was updated to estimate the long-term health outcomes of lecanemab plus standard of care (SoC) compared to SoC alone in patients with early AD and evidence of brain amyloid burden, using recent phase III trial data and published literature. The disease progression is described by changes in the underlying biomarkers of AD, including measures of amyloid and tau, and their connection to the clinical presentation of the disease assessed through various patient-level scales of cognition and function.

Results: Lecanemab treatment was estimated to slow the progression of AD to moderate and severe stages and reduce the time spent in these more advanced states. In individuals with early AD, lecanemab plus SoC was associated with a gain of 0.71 quality-adjusted life-years (QALYs), a 2.95-year delay in mean time to progression to AD dementia, a reduction of 0.11 years in institutional care, and an additional 1.07 years in community care as shown in the base-case study. Improved health outcomes were demonstrated with lecanemab treatment when initiated earlier based on age, disease severity, or tau pathology, resulting in estimated gains in QALYs ranging from 0.77 to 1.09 years, compared to 0.4 years in the mild AD dementia subset, as shown by the model.

Conclusion: The study findings demonstrate the potential clinical value of lecanemab for individuals with early AD by slowing down disease progression and prolonging time in earlier stages of disease, which significantly benefits not only patients and caregivers but also society overall.

Trial registration: ClinicalTrials.gov identifier, NCT03887455.

Keywords: Alzheimer’s disease; Delay of onset; Disease-modifying therapy; Institutionalization; Lecanemab; Progression; Simulation.

Fig. 1

Amyloid PET SUVr and CDR-SB trajectories. Calibration of treatment effect on amyloid level during and beyond trial time horizon. AD ACE = Alzheimer’s disease Archimedes condition-event, CDR-SB = Clinical Dementia Rating Scale-Sum of Boxes, PET = positron emission tomography, SoC = standard of care, SUVr = standard uptake value ratio

Fig. 2

Patient distribution in health states with the use of SoC or lecanemab + SoC. MCI = mild cognitive impairment, SoC = standard of care, Tx = treatment