The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for the approval of lecanemab in the European Union. This decision supports the use of lecanemab for treating early Alzheimer's disease in adult patients who are either apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers. The recommendation follows Eisai’s request for a re-examination of the CHMP’s earlier negative recommendation.
The CHMP recommends lecanemab for patients with mild cognitive impairment (MCI) and mild dementia caused by Alzheimer's disease, specifically those who carry one copy (heterozygotes) or do not carry the Apolipoprotein E ε4 (ApoE ε4) gene. A final decision from the European Commission is anticipated within 67 days.
Clinical Trial Data
The CHMP's positive opinion is 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 (MCI or mild dementia due to AD, confirmed by amyloid pathology). Of these, 1,521 were ApoE ε4 heterozygotes or non-carriers, aligning with the recommended indicated population in the EU. Participants were randomized 1:1 to receive either lecanemab 10 mg/kg bi-weekly or placebo for 18 months.
The primary endpoint was the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a global cognitive and functional scale. In the Clarity AD trial, lecanemab reduced clinical decline on CDR-SB by 33% at 18 months compared to placebo in the recommended indicated population (p<0.00001). The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.15 with lecanemab and 1.73 with placebo (difference, −0.58; 95% confidence interval [CI], −0.81 to −0.35).
Impact on Daily Living
Secondary endpoints also demonstrated significant benefits. The Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which assesses the ability of patients to function independently, showed 39% less decline compared to placebo at 18 months (p<0.00001). The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.7 in the placebo group (difference, 2.2; 95% CI, 1.3 to 3.1).
Safety Profile
The most common adverse reactions observed in the recommended indicated population were infusion-related reactions (26%), ARIA-H (amyloid-related imaging abnormalities-hemosiderin deposition) (13%), fall (11%), headache (11%), and ARIA-E (amyloid-related imaging abnormalities-edema) (9%).
Commercialization and Future Steps
Lecanemab is already approved in the US, Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain. Eisai is responsible for the clinical development, market approval applications, and commercialization of lecanemab globally. BioArctic retains the rights to commercialize lecanemab in the Nordic region and is preparing for joint commercialization with Eisai, pending approval from the European Commission.
Gunilla Osswald, CEO of BioArctic, stated, “We are very happy and grateful that the CHMP, during their re-examination of lecanemab, has recognized that for the patients in this population, the benefit of the treatment is greater than the risk. We now look forward to the European Commission’s decision that is the next step towards providing access to this new treatment for patients in Europe with Alzheimer’s disease.”
Eisai has also submitted applications for regulatory approval of lecanemab in 17 other countries and regions. A supplemental Biologics License Application (sBLA) for less frequent intravenous maintenance dosing was submitted to the U.S. Food and Drug Administration (FDA) in March 2024, which was accepted in June 2024. In October 2024, the rolling submission of a Biologics License Application (BLA) for maintenance dosing of a subcutaneous injection formulation was completed in the U.S. under Fast Track status.
