The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending the approval of lecanemab (Leqembi; Eisai) for the treatment of early-stage Alzheimer's disease (AD). This decision reverses an earlier negative opinion from the agency.
The European Commission is expected to make a final decision on lecanemab’s marketing authorization application (MAA) within 67 days of the CHMP recommendation. Lecanemab, a monoclonal antibody, selectively binds to soluble amyloid-β (Aβ) aggregates and has been available in the US since 2023, following traditional FDA approval.
The CHMP's positive opinion was primarily influenced by data from the Phase 3 Clarity AD trial (NCT03887455). In this global, placebo-controlled, double-blind study, lecanemab met its primary endpoint, demonstrating a significant change in Clinical Global Dementia-Sum of Boxes (CDR-SB) score over 18 months compared to placebo. The study involved 1795 patients with early AD, with 1521 in the recommended indicated population (apolipoprotein E4 non-carriers or heterozygotes).
Clarity AD Trial Results
Led by Christopher van Dyck, MD, the Clarity AD trial showed that lecanemab treatment resulted in a statistically significant 27% reduction in CDR-SB scores compared to placebo over the 18-month period. The drug also met key secondary endpoints, including a significant reduction in amyloid PET centiloids (LS difference: –50.12; P < .0001) and improved scores on the Alzheimer’s Disease Assessment Scale-Cognitive 14 (LS difference: –1.442; P = .00005) compared to placebo over 18 months. Lecanemab also outperformed placebo on the Alzheimer's Disease Composite Scale (ADCOMS; LS difference: –0.00; P = .00002) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS MCI-ADL; LS difference: 2.016; P < .00001). Specifically, it slowed disease progression by 24% on ADCOMS and by 37% on ADCS MCI-ADL at the same time point.
Global Regulatory Landscape
Lecanemab has received approval in several countries, including Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, and Great Britain. However, the Therapeutic Goods Administration of Australia recently decided against registering lecanemab for early-stage AD, citing concerns that the observed reduction in disease progression did not outweigh the safety risks.
Alternative Dosing and Administration
Eisai is actively pursuing alternative methods to improve lecanemab administration and dosing. The FDA has accepted a supplemental biologics license application (sBLA) for a new monthly intravenous maintenance dosing option, with a decision expected by January 25, 2025. Additionally, Eisai has submitted a BLA for a subcutaneous autoinjector formulation of lecanemab, potentially offering a more convenient administration method for patients at home or in medical facilities. Analysis of Clarity AD data suggests that subcutaneous lecanemab demonstrated greater amyloid plaque removal compared to the approved biweekly intravenous administration, while maintaining bioequivalence in pharmacokinetic exposure.
