Simulation of long-term lecanemab treatment effect on Alzheimer's disease progression

Anti-amyloid therapies such as lecanemab have demonstrated statistically significant slowing of decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in patients with early Alzheimer's disease (AD) in pivotal trials. Converting treatment differences on CDR-SB into time saved from disease progression may help convey clinical relevance for patients and caregivers more effectively.

Disease progression models were developed using Alzheimer's Disease Neuroimaging Initiative and National Alzheimer's Coordinating Center data. A 37% treatment-related time delay, derived from the Clarity AD trial, was applied to estimate long-term efficacy of lecanemab.

Natural progression models estimated 11.5 to 13.7 years from mild cognitive impairment due to AD to severe AD. When starting treatment at CDR-SB 3.2, lecanemab delayed progression to severe AD by 2.5 to 3.7 years when assuming patients remained on treatment and 2.0 to 3.0 years when accounting for treatment discontinuation. Results were consistent across different datasets.

Projections suggest lecanemab substantially delays clinical progression of AD, preserving patients' time in earlier stages of AD.