Long-term lecanemab reduces cognitive decline in early Alzheimer’s disease

Treatment with lecanemab continue to provide benefits to patients with early Alzheimer’s disease (AD) through 24 months, according to the results of the ongoing open-label extension study of Clarity AD. Those who have been treated much later also show disease improvements.

“Treatment differences with ongoing lecanemab treatment through 30 months, relative to the newly treated lecanemab participants, is consistent with a disease-modifying effect,” said lead study author Christopher van Dyck from the Yale School of Medicine, New Haven, Connecticut, US.

“Delayed start and lower pathology group results support early initiation of treatment with lecanemab,” he added.

Van Dyck reported the initial findings from the ongoing lecanemab Clarity AD OLE study at the recent AAN 2024 Annual Meeting. In this study, he and his team determined whether the treatment benefits of lecanemab persisted through 30 months in patients with early AD.

The OLE assessed both clinical (ie, CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL) and biomarker (ie, PET, Aβ42/40 ratio, and ptau181) outcomes by examining the two cohorts involved: delayed start (core: placebo, followed by OLE: lecanemab) and early start (core: lecanemab, followed by OLE: lecanemab). The research team performed analyses by core baseline tau PET levels from the tau PET substudy.

A total of 1,385 patients with early AD participated in the OLE. Those who received lecanemab initially consistently showed improvements in clinical endpoints through 24 months. [Van Dyck, et al, AAN 2024]

Separation between early and delayed start of lecanemab treatment remained between 18 and 24 months (p<0.05). Disease trajectory followed a similar pattern when all participants received lecanemab. Changes in biomarker outcomes also exhibited improvements, which were noted in as early as 3 months among patients in the delayed start cohort.

“Across assessments, consistent rates of clinical stability or improvements were observed regardless of baseline tau levels, with the highest rates of improvements observed for the low tau group at 24 months (no decline: 79 percent; improvement: 50 percent),” van Dyck said.

Clarity AD

“Lecanemab is an antiamyloid monoclonal antibody that binds with highest affinity to soluble Aβ protofibrils, which are more toxic than monomers or insoluble fibrils/plaque,” according to the researchers.

In Clarity AD, an 18-month, phase III randomized controlled trial, lecanemab resulted in decreased markers of brain amyloid in early AD. Patients treated with lecanemab exhibited moderately less decline in cognition and function compared with those who received placebo (difference, −59.1 centiloids; 95 percent confidence interval [CI], −62.6 to −55.6). [N Engl J Med 2023;388:9-21]

Mean differences in the change from baseline between the two groups also favoured lecanemab: ADAS*-cog14 score (difference, ‒144, 95 percent CI, ‒2.27 to ‒0.61; p<0.001); ADCOMS** (difference, ‒0.050, 95 percent CI, ‒0.074 to ‒0.027; p<0.001); and ADCS-MCI-ADL*** score (difference, 2.0, 95 percent CI, 1.2‒2.8; p<0.001).

However, treatment with lecanemab also correlated with some adverse events, such as infusion-related reactions in 26.4 percent of the participants and amyloid-related imaging abnormalities with oedema or effusions in 12.6 percent.

*Alzheimer’s Disease Assessment Scale

**Alzheimer’s Disease Composite Score

***Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment