Eisai Gets EU CHMP Approval for Lecanemab in Early Alzheimer's

Eisai Co., Ltd., headquartered in Tokyo and led by CEO Haruo Naito, alongside Biogen Inc., based in Cambridge, Massachusetts, and headed by CEO Christopher A. Viehbacher, announced a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the amyloid-beta (Aβ) monoclonal antibody, lecanemab. This recommendation is for the treatment of adult patients with a clinical diagnosis of mild cognitive impairment and mild dementia due to Alzheimer's disease (Early Alzheimer's disease) who are non-carriers or heterozygotes for apolipoprotein E ε4 (ApoE ε4) with confirmed amyloid pathology. Eisai had previously requested a re-examination following a negative opinion from the CHMP in July 2024. The European Commission is expected to make a final decision on the marketing authorization application (MAA) for lecanemab within 67 days based on this positive CHMP opinion.

Lecanemab works by selectively binding to soluble Aβ aggregates (protofibrils) and insoluble Aβ aggregates (fibrils), which are significant components of Aβ plaques in Alzheimer's disease (AD). This binding results in the reduction of both Aβ protofibrils and Aβ plaques in the brain. Approximately 6.9 million people in Europe are currently affected by AD, a number projected to nearly double by 2050 due to aging populations. AD progresses through stages that increase in severity, presenting various challenges for patients and their caregivers. There is a substantial need for new treatment options that can slow the progression of early AD and reduce the burden on affected individuals and society.

Eisai leads the development and regulatory submissions for lecanemab globally, with both Eisai and Biogen co-commercializing and co-promoting the product. Eisai holds the final decision-making authority.

Lecanemab, also known by its brand name Leqembi, is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody targeting aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). The CHMP's positive opinion in the EU was primarily based on data from Eisai's global Clarity AD Phase 3 clinical trial. This trial showed that lecanemab met its primary and all key secondary endpoints with statistically significant results. The Clarity AD study was a global, placebo-controlled, double-blind, randomized trial involving 1,795 patients with early AD (mild cognitive impairment or mild dementia due to AD with confirmed amyloid pathology), with 1,521 of these patients being non-carriers or heterozygotes for ApoE ε4.

The primary endpoint was the global cognitive and functional scale, CDR-SB. Lecanemab reduced clinical decline on the CDR-SB by 31% at 18 months compared to placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups, and the adjusted least-squares mean change from baseline at 18 months was 1.217 for the lecanemab group and 1.752 for the placebo group. CDR-SB measures six domains of functioning, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.

The secondary endpoint, measured by the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), showed 33% less decline compared to placebo at 18 months. The ADCS-MCI-ADL assesses patients' ability to function independently, including dressing, feeding themselves, and participating in community activities.

In the population of ApoE ε4 heterozygotes or non-carriers, common adverse reactions included infusion-related reactions (26%), ARIA-H (13%), headache (11%), and ARIA-E (9%).

Lecanemab has been approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, the UAE, and Great Britain, and is under regulatory review in 17 other countries. A supplemental Biologics License Application (sBLA) for intravenous maintenance dosing was submitted to the U.S. Food and Drug Administration (FDA) in March 2024 and accepted in June 2024. In May 2024, an application for a subcutaneous injection formulation was initiated in the U.S. under Fast Track status, with completion in October 2024.

Since July 2020, the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD has been ongoing. Additionally, since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD) has been underway, including lecanemab as the backbone anti-amyloid therapy. This study is led by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University School of Medicine in St. Louis and is conducted as a public-private partnership involving the Alzheimer's Clinical Trial Consortium, funded by the National Institute on Aging, a part of the National Institutes of Health, Eisai, and Biogen.