Eisai and Biogen announced that 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). The recommendation applies to patients who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes with confirmed amyloid pathology. Eisai had requested a re-examination of the prior negative opinion adopted by the CHMP in July 2024.
Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody designed to selectively bind to soluble amyloid-beta (Aβ) aggregates (protofibrils) and insoluble Aβ aggregates (fibrils). By targeting both forms of Aβ, lecanemab aims to reduce Aβ protofibrils and plaques in the brain.
The CHMP's positive opinion is primarily based on data from Eisai's Phase 3 Clarity AD clinical trial. This global, placebo-controlled, double-blind study involved 1,795 patients with early Alzheimer's disease, with 1,521 in the recommended indicated population (ApoE ε4 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. In the recommended population, lecanemab treatment resulted in a 31% reduction in clinical decline on the CDR-SB scale at 18 months compared to placebo (P=0.00001). The adjusted least-squares mean change from baseline at 18 months was 1.217 with lecanemab and 1.752 with placebo (difference, −0.535; 95% confidence interval [CI], −0.778 to −0.293).
Additional Trial Data
Secondary endpoints from the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) also favored lecanemab. This scale, which measures information provided by caregivers, showed 33% less decline in the lecanemab group compared to placebo at 18 months (P=0.00002). The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.873 in the lecanemab group and −5.809 in the placebo group (difference, 1.936; 95% CI, 1.029 to 2.844).
Safety Profile
The most common adverse reactions observed in ApoE ε4 heterozygotes or non-carriers treated with lecanemab were infusion-related reactions (26%), ARIA-H (13%), headache (11%), and ARIA-E (9%).
Regulatory Status and Future Studies
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 and Biogen are also studying lecanemab in earlier stages of Alzheimer's disease, including preclinical AD (AHEAD 3-45 study) and dominantly inherited AD (Tau NexGen study).
Alzheimer's Disease Burden
Alzheimer's disease affects an estimated 6.9 million people in Europe, with projections indicating a near doubling of this figure by 2050. The progressive nature of the disease presents significant challenges for patients and their caregivers, highlighting the urgent need for new treatments that can slow disease progression and reduce the overall burden on affected individuals and society.
