Estimate the 10-year time-savings benefits of lecanemab in early AD, to provide clarity on long-term benefits of continuous treatment and provide meaningful information for clinical decision-making.

Lecanemab is an Ab-targeting therapy that slows the rate of cognitive and functional decline in early Alzheimer's disease (AD). The CLARITY-AD OLE showed 11 months of time saved with 48 months of treatment, but the benefits beyond 48 months remain unknown.

Observational ADNI data was used to model progression curves in untreated AD patients through the course of their disease. 48-month CLARITY-AD OLE data was used to modify progression curves and estimate benefits of treatment over 10 years. The slowing rates of progression were estimated by a Bayesian Gaussian Process model fitted on summarized data from 19 studies of Ab therapies, then adjusted to the slowing rates observed with lecanemab. This model accounted for AD severity at initiation and treatment duration. Slowing rates after discontinuation were estimated using data from the 19 studies, where a decrease in accumulating benefit was observed post-stopping.

Our results validate previous time-saved estimates from CLARITY-AD OLE. When treatment begins at MCI and mild stages, ongoing lecanemab therapy for 10-years is estimated to delay progression by 2.5-years, and stopping after 1 year delays progression by 1-year over 10-years. Based on data from the low-amyloid group, 10 years of continuous treatment with lecanemab is projected to achieve 4.4 years of time savings compared to 1.8 years if stopped at 1 year. Overall, an individual treated for 10 years is projected to have 44% less disease progression.

Models from low-amyloid groups suggest that treating with lecanemab at the earliest signs of disease will lead to the greatest delay of disease progression. Each additional year on lecanemab could further delay progression compared to stopping treatment, even after plaque is cleared.