The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of lecanemab for the treatment of adult patients with mild cognitive impairment and mild dementia due to Alzheimer's disease (early Alzheimer's disease). This decision specifically targets patients who are apolipoprotein E e4 (ApoE e4) non-carriers or heterozygotes with confirmed amyloid pathology. Eisai Co., Ltd. and Biogen Inc. jointly announced this development, marking a significant step toward addressing the unmet needs in early Alzheimer's treatment.
Mechanism of Action
Lecanemab is a monoclonal antibody designed to selectively bind to soluble amyloid-beta (Aβ) aggregates, also known as protofibrils, as well as insoluble Aβ aggregates (fibrils). These aggregates are major components of Aβ plaques found in the brains of Alzheimer's patients. By targeting both protofibrils and plaques, lecanemab aims to reduce their presence in the brain, potentially slowing the progression of the disease.
Clinical Trial Data
The CHMP's positive opinion was primarily based on data from Eisai's global Phase 3 Clarity AD clinical trial. This study enrolled 1,795 patients with early Alzheimer's disease, with 1,466 in the recommended indicated population (ApoE e4 non-carriers or heterozygotes). Participants were randomized 1:1 to receive either lecanemab 10 mg/kg bi-weekly or placebo for 18 months.
The primary endpoint of the Clarity AD trial was the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale, a global cognitive and functional assessment tool. Results showed that lecanemab reduced clinical decline by 31% at 18 months compared to placebo (difference, −0.535; 95% confidence interval [CI], −0.778 to −0.293; P=0.00001). The mean CDR-SB score at baseline was approximately 3.2 in both groups. Key secondary endpoints also demonstrated statistically significant benefits, including a 33% less decline in the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) at 18 months (difference, 1.936; 95% CI, 1.029 to 2.844; P=0.00002).
Alzheimer's Disease Burden
Alzheimer's disease currently affects an estimated 6.9 million people in Europe, and this number is projected to nearly double by 2050 due to aging populations. The progressive nature of AD presents significant challenges for patients and their caregivers, highlighting the urgent need for effective treatments that can slow disease progression and reduce the overall burden on affected individuals and society.
Safety and Regulatory Status
In the ApoE e4 heterozygotes or non-carriers population, the most common adverse reactions observed in the Clarity AD trial were infusion-related reactions (26%), ARIA-H (amyloid-related imaging abnormalities with hemorrhage, 13%), headache (11%), and ARIA-E (amyloid-related imaging abnormalities with edema, 9%).
Lecanemab has already been approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain. It is currently under regulatory review in 17 other countries. Eisai serves as the lead for lecanemab's development and regulatory submissions globally, with Eisai and Biogen co-commercializing and co-promoting the product. Eisai retains final decision-making authority.
