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Lecanemab may slow decline of cognition and function in AD

Presented By
Prof. Christopher van Dyck, Yale School of Medicine, USA
AAN 2023

In the placebo-controlled CLARITY AD study, lecanemab slowed the decline in measures of cognition and function, and reduced markers of amyloid in early Alzheimer’s disease (AD) at 18 months. Lecanemab improving amyloid and tau indicates disease modification.

The study results were presented by Prof. Christopher van Dyck (Yale School of Medicine, USA). He said that the accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate AD pathology. Lecanemab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that highly selectively binds to Aβ aggregate species and initiates microglial-mediated clearance of protofibrils and plaques.

CLARITY AD (NCT03887455) is a global, double-blind, parallel-group phase 3 trial in which lecanemab is tested against placebo in participants with early AD [1]. The 1795 participants were 50 to 90 years of age with mild cognitive impairment or mild dementia due to AD, with confirmed amyloid pathology. In the 18-months randomisation phase, they were assigned 1:1 to receive intravenous lecanemab 10 mg/kg biweekly (n=898), or a matching placebo (n=897). In the open-label extension phase, all participants receive lecanemab. The primary endpoint was the change after 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18).

The mean CDR-SB score at baseline was ~3.2 in both groups. Lecanemab significantly slowed disease progression on CDR-SB by 27% at 18 months, and at all time points beginning at 6 months. The adjusted least-squares mean change from baseline was 1.21 in the lecanemab group versus 1.66 in the placebo group (difference −0.45; 95% CI, −0.67 to −0.23; P<0.001). A slope analysis using CDR-SB showed a 32% annual slowing of the slope (95% CI, 18% to 46%; P=0.00001) compared to placebo. This means that the lecanemab group took 25.5 months to reach the same level as placebo at 18 months.

In an exploratory analysis, lecanemab also showed consistent benefits in health-related quality of life measures and caregiver burden across different scales, Prof. Van Dyck added. The safety profile of lecanemab was acceptable. Lecanemab resulted in infusion-related reactions in 26.4% of patients and amyloid-related imaging abnormalities with oedema or effusions (ARIA-E) in 12.6%.

Biomarker studies, using PET, CSF, and plasma analyses, revealed that lecanemab improved both essential biological features of AD, amyloid and tau. This indicated disease modification, which Prof. Van Dyck said was “unprecedented” in AD. The AHEAD study is now evaluating whether earlier (presymptomatic) and longer intervention may be associated with greater effect size.


    1. Van Dyck CH. A study to confirm safety and efficacy of lecanemab in participants with early Alzheimer’s disease (CLARITY AD). PL5.005, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.


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