EU’s CHMP Reaffirms Positive Opinion of Alzheimer Treatment Lecanemab

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Lecanemab, a monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid-ß, remains under review, with a decision expected in the coming months.

According to a recent announcement, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) reasserted stance on its recent positive opinion of lecanemab (Leqembi; Eisai), an antiamyloid therapy for patients with early-stage Alzheimer disease (AD). The European Commission (EC) is expected to continue its review of the therapy, and, if approved, the therapy would become available to all 27 European Union member states.¹

In January, as part of its decision-making process, the EC asked the CHMP to consider information on the safety of lecanemab that became available after the adoption of the CHMP opinion in November 2024 and whether this may require an update of the opinion, and to consider whether the wording of the risk minimization measures in the opinion is clear enough to ensure correct implementation. After reviewing the additional information, the CHMP concluded that its positive opinion for lecanemab does not need to be updated.

Lecanemab, a humanized immunoglobulin gamma 1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid-ß (Aß), was approved under traditional approved by the EMA on January 12, 2023, for the treatment of AD, days after the FDA made its decision to approve the therapy. It is approved in several other countries, including Japan, China, South Korea, Israel, the United Arab Emirates, Mexico, Macau and Oman, and remains under review in 18 countries and regions including the EU.

The therapy’s EU submission was primarily based on data from the pivotal phase 3 Clarity AD trial (NCT03887455), a double-blind, placebo-controlled trial that served as supportive evidence for the drug’s traditional approval in the U.S. Across an 18-month treatment period, the antiamyloid treatment met its primary end point of change in Clinical Global Dementia-Sum of Boxes (CDR-SB) score, demonstrating a statistically significant 27% reduction relative to placebo.²

The study, a 1795-patient cohort, also showed that lecanemab met secondary end points. Over the 18-month timeframe, investigators observed a significant reduction in amyloid PET centiloids (least square [LS] mean difference, –50.12; P < .0001) and improved scores on the Alzheimer’s Disease Assessment Scale-Cognitive 14 (LS difference: –1.442; P = .00005). It also outperformed placebo on both the Alzheimer's Disease Composite Scale (ADCOMS) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS MCI-ADL), slowing disease progression by 24% on ADCOMS (LS difference: –0.00; P = .00002) and by 37% on ADCS MCI-ADL (LS difference: 2.016; P < .00001).

Antiamyloid treatments like lecanemab target amyloid plaques, which are abnormal clumps of protein that accumulate in the brains of people with AD. These plaques are one of the hallmark features of AD and are believed to contribute to cognitive decline and neurodegeneration.

The first approved antiamyloid was aducanumab (Aduhelm; Biogen); however, the drug was removed from market years later following controversy and scrutiny with its approval and rollout process. In July 2024, donanemab (Kisulna; Eli Lilly) hit the market as the third approved antiamyloid therapy, becoming the first to show evidence that supports stopping treatment when amyloid plaques are removed. The 3 therapies differ slightly in their mechanism of action, despite being antiamyloid treatments. Lecanemab focuses on soluble, oligomeric forms of Aß, aducanumab targets aggregated Aß plaques, and donanemab targets a specific epitope of Aß, which is the N-terminal part of the amyloid protein that is found in the more toxic, aggregated forms of amyloid plaques.

REFERENCES
1. The Committee for Medicinal Products for Human Use (CHMP) Reaffirms Positive Opinion for Lecanemab in Early Alzheimer's Disease. News release. Eisai. February 28, 2025. Accessed March 6, 2025. https://www.prnewswire.com/news-releases/the-committee-for-medicinal-products-for-human-use-chmp-reaffirms-positive-opinion-for-lecanemab-in-early-alzheimers-disease-302388596.html
2. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9-21. doi:10.1056/NEJMoa2212948