Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease.

Abstract

Objective: To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease.

Data sources: A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references.

Study selection and data extraction: We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease.

Data synthesis: In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; P < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%).

Relevance to patient care and clinical practice: Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions.

Conclusion: Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aβ) aggregates. Lecanemab has exhibited a decrease in brain Aβ plaques and moderately less decline on clinical measures of cognitive function.