Lecanemab in Early Alzheimer's Disease
The accumulation of soluble and insoluble aggregated amyloid-beta (Abeta) may initiate or potentiate pathologic processes in Alzheimer's disease (1).
Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Abeta soluble protofibrils.
A randomised controlled trial RCT (n=1,795) found 2-weekly infusions of the humanized IgG1 monoclonal antibody Lecanemab reduced rate of cognitive decline vs placebo at 18 months (Clinical Dementia Rating-Sum of Boxes (CDR-SB) score [range 0-18] increase of 1.21 vs 1.66, p<0.001)
- an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing
- participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab (10 mg per kilogram of body weight every 2 weeks) or placebo
- primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment)
- mean CDR-SB score at baseline was approximately 3.2 in both groups
- in a substudy involving 698 participants
- there were greater reductions in brain amyloid burden with lecanemab than with placebo (difference, -59.1 centiloids; 95% CI, -62.6 to -55.6)
- lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with oedema or effusions in 12.6%
- study authors concluded:
- Lecanemab reduced markers of amyloid in early Alzheimer's disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events.
Reference:
- van Dyck CH et al. Lecanemab in Early Alzheimer's Disease. NEJM November 29, 2022.