Leqembi Treatment Associated with Sustained Reduction in Cognitive Decline According to 3-Year OLE Results

New 3-year open-label extension (OLE) results from the Clarity AD clinical trial (NCT03887455) presented at the 2024 meeting of the Alzheimer’s Association International Conference (AAIC) showed sustained reductions in cognitive decline in participants with early Alzheimer disease (AD) treated with Leqembi (lecanemab-irmb; Eisai, Tokyo, Japan; Biogen, Cambridge, MA). Leqembi is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble forms (oligomers and protofibrils) and insoluble forms (fibrils) of Aβ.

The multicenter, double-blind, phase 3 Clarity AD trial included 1795 participants aged 50 to 90 years with early AD. Participants were randomly assigned 1:1 to receive either intravenous Leqembi (10 mg/kg of body weight every 2 weeks) or placebo; 95% of trial participants either continued or began Leqembi treatment in the OLE. The OLE assessed the change in Clinical Dementia Rating Sum of Boxes (CDR-SB) from baseline to 36 months; additional assessments included biomarker and cognitive testing. Researchers selected Alzheimer’s Disease Neuroimaging Initiative (ADNI) observational cohort participants who matched the Clarity AD participants in baseline demographics and characteristics for the comparator group.

• Participants treated with Leqembi experienced a reduction in clinical decline on the CDR-SB by -0.95 points compared to the expected decline based on the matched ADNI cohort.
• 58% of patients with no/very low tau levels showed improvement or no decline on CDR-SB after 3 years of continuous treatment with Leqembi compared to the expected decline based on the matched ADNI cohort.
• Participants who switched from placebo to Leqembi during the OLE showed improvement in amyloid-related biomarkers within 3 months of treatment initiation.