Abstract Details

Lecanemab is an anti-amyloid monoclonal antibody that binds with highest affinity to soluble Aβ protofibrils, which are more toxic than monomers or insoluble fibrils/plaque. In the 18-month phase 3 Clarity AD study, lecanemab demonstrated a consistent slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early AD.

To report the initial findings from the ongoing lecanemab Clarity AD open-label extension (OLE) study, in which we evaluated whether the treatment benefits were maintained up to 30 months in participants with early Alzheimer’s disease (AD).

Clarity AD is an 18-month, randomized study (core) in patients with early AD, with an OLE phase where eligible participants received open-label lecanemab. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL) and biomarker (PET, Aβ42/40 ratio, and ptau181) outcomes were evaluated overall and by examining ‘delayed start’ (core:placebo followed by OLE:lecanemab) and ‘early start’ (core:lecanemab followed by OLE:lecanemab) cohorts. Analyses by core baseline tau PET levels were conducted from the tau PET sub-study.

Overall, 1385 participants enrolled in the OLE. Across clinical endpoints, lecanemab-treated participants continued to benefit through 24 months. Separation between early and delayed start was maintained between 18 and 24 months (p<0.05), with a similar disease trajectory when all participants received lecanemab. Biomarker changes continued to improve and were seen in as early as 3 months in newly-treated lecanemab participants. Across assessments, consistent rates of clinical stability or improvements were observed regardless of baseline tau levels, with the highest rates of improvements observed for the low tau group at 24 months (no decline:79%; improvement:50%). Preliminary 30-month data will be presented.

Treatment differences with ongoing lecanemab treatment through 30 months, relative to the newly treated lecanemab participants, is consistent with a disease-modifying effect. Delayed start and lower pathology group results support early initiation of treatment with lecanemab.