Lecanemab—Monoclonal Antibodies for the Treatment of Early Alzheimer’s Disease

Objective: Review the pharmacology, efficacy, and safety of lecanemab, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody, for the treatment of early Alzheimer’s disease (AD). Data Sources: Comprehensive search of Embase, PubMed, International Pharmaceutical Abstracts, Cochrane CENTRAL, Scopus, Web of Science, and Google Scholar were conducted from inception through December 2025. Study Selection and Data Extraction: Phase I-III clinical trials, systematic reviews, and meta-analyses evaluating lecanemab pharmacology, pharmacokinetics, efficacy, and safety were included. Product labeling was reviewed to supplement clinical data. Data synthesis: In the phase III Clarity AD trial, patients were randomized 1:1 to lecanemab 10 mg/kg every 2 weeks or placebo. The primary endpoint was change from baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) score at 18 months. Lecanemab demonstrated a mean change of 1.21 versus 1.66 with placebo (difference, −0.45; 95% CI, −0.67 to −0.23; P < .001). Secondary endpoint, amyloid burden via positron emission tomography (PET) scans ( n = 698) showed −55.48 centiloids with lecanemab versus 3.64 with placebo (difference −59.12 centiloids; 95% CI, −62.64 to −55.6; P < .001). Additional endpoints included changes in ADAS-cog 14, ADCOMS, and ADCS-MCI-ADL scores favoring lecanemab over placebo. Lecanemab was well tolerated; infusion site reactions occurred in 26.4%. Amyloid-related imaging abnormalities (ARIA-E) occurred in 12.6% of participants. Conclusion: Compared to placebo, lecanemab demonstrated statistically significant slowing of cognitive decline on CDR-SB and secondary endpoints, including amyloid burden reduction. However, its clinical benefit must be weighed against ARIA risk and substantial financial burden. Current evidence supports its use in carefully selected patients with early AD under close supervision.