The Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for the approval of lecanemab in the European Union, marking a significant step forward in the treatment of early Alzheimer's disease. The recommendation applies to adult patients with mild cognitive impairment (MCI) or mild dementia caused by Alzheimer's who are apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers. This decision follows Eisai's request for a re-examination of the CHMP's earlier negative recommendation.
The expected decision from the European Commission within 67 days could pave the way for broader access to this novel treatment. Gunilla Osswald, CEO at BioArctic, expressed gratitude that the CHMP recognized the benefit of lecanemab outweighs the risk for the indicated patient population.
Clinical Trial Data and Efficacy
The CHMP's recommendation is supported by Phase 3 data from Eisai's global Clarity AD clinical trial. The trial included 1,795 patients with early Alzheimer's, with 1,521 in the recommended indicated population (ApoE ε4 heterozygotes or non-carriers). Patients were administered 10 mg/kg of lecanemab bi-weekly or placebo for 18 months.
The primary endpoint, the Clinical Dementia Rating-Sum of Boxes (CDR-SB), showed a 33% reduction in clinical decline at 18 months compared to placebo (difference, -0.58; 95% confidence interval [CI], -0.81 to -0.35; P<0.00001). The Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) also demonstrated 39% less decline compared to placebo (difference, 2.2; 95% CI, 1.3 to 3.1; P<0.00001).
Lecanemab's Mechanism of Action
Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody that targets aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). It is designed to reduce amyloid plaques in the brain, a hallmark of Alzheimer's disease.
Global Regulatory Status and Ongoing Studies
Lecanemab is already approved in the U.S., Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain. Eisai has also submitted applications for regulatory approval in 17 other countries and regions, including the European Union. Eisai's Phase 3 clinical study (AHEAD 3-45) with lecanemab in individuals with preclinical AD is ongoing, with full recruitment achieved in October 2024. Additionally, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD) includes lecanemab as the backbone anti-amyloid therapy.
Safety Profile
The most common adverse reactions observed in the recommended indicated population (ApoE ε4 heterozygotes or non-carriers) were infusion-related reactions (26%), ARIA-H (13%), fall (11%), headache (11%), and ARIA-E (9%).
