Topline results were announced from a large global phase 3 confirmatory study of lecanemab for the treatment of early Alzheimer disease.

Lecanemab is a humanized monoclonal antibody that works by selectively binding to, neutralizing and eliminating soluble toxic amyloid beta aggregates. The investigational agent was granted Priority Review by the Food and Drug Administration (FDA) in July 2022 for the treatment of mild cognitive impairment due to Alzheimer disease (AD) and early AD with confirmed presence of amyloid pathology in the brain.

The confirmatory trial, Clarity AD (ClinicalTrials.gov Identifier: NCT03887455), included 1795 patients with early AD. Patients were randomly assigned 1:1 to receive lecanemab at a dosage of 10mg/kg biweekly administered as intravenous infusion or placebo. The primary endpoint of the study was the change from baseline in CDR-SB (Clinical Dementia Rating-Sum of Boxes), a numeric scale used to quantify the various severity of symptoms of dementia, at 18 months.

Findings showed a statistically significant treatment difference in the CDR-SB score change (-0.45; P =.00005), indicating a reduction in clinical decline of 27%, compared with placebo. Highly statistically significant changes in CDR-SB were observed as early as 6 months.

Results also showed statistically significant improvements in all key secondary endpoints compared with placebo (P <.01), including changes in amyloid levels in the brain (as measured by amyloid positron emission tomography), the AD Assessment Scale-Cognitive Subscale 14, the AD Composite Score, and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment.

As for safety, the total incidence of amyloid-related imaging abnormalities (ARIA-E [edema/effusion] and/or ARIA-H [cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis]) was 21.3% in the lecanemab group and 9.3% in the placebo group, which was noted to be within expectations.

According to the FDA, the Clarity AD trial will serve as the confirmatory study to verify the clinical benefit of lecanemab. A decision on the Biologics License Application, which includes data from a phase 2b study (ClinicalTrials.gov Identifier: NCT01767311), is expected on January 6, 2023.

Reference

Lecanemab confirmatory phase 3 Clarity AD study met primary endpoint, showing highly statistically significant reduction of clinical decline in large global clinical study of 1,795 participants with early Alzheimer’s disease. News release. September 28, 2022. https://www.prnewswire.com/news-releases/lecanemab-confirmatory-phase-3-clarity-ad-study-met-primary-endpoint-showing-highly-statistically-significant-reduction-of-clinical-decline-in-large-global-clinical-study-of-1-795-participants-with-early-alzheimers-disease-301634888.html