▎WuXiEdited by Kant Content Team

Eisai and Biogen recently announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of their Alzheimer's disease (AD) therapy, Leqembi (lecanemab), for the treatment of adult patients with mild cognitive impairment and mild dementia (early Alzheimer's disease) caused by clinically diagnosed Alzheimer’s disease. These patients are carriers of the apolipoprotein E ε4 allele (ApoE ε4) Non-carriers or heterozygotes, with definitive amyloid pathology.

Amyloid-Related Imaging Abnormalities (ARIA) are targetedβCommon adverse reactions of AD therapy targeting amyloid protein. It mainly manifests in two forms: ARIA-E (edema), which is fluid accumulation in the brain; and ARIA-H (hemorrhage), which is minor bleeding in the brain. Many Alzheimer's patients naturally exhibit these symptoms, but those receiving targetedβAmyloid therapy may worsen patients' symptoms. Eisai requested a re-evaluation after the CHMP issued a negative opinion in July 2024 on Leqembi's approval for treating all early-stage Alzheimer's patients.CHMP considered the analysis of patient subgroups, and this application excluded those carrying twoApoE ε4Data from patients with allele copies indicate that these patients are at the highest risk of developing ARIA.

The analysis results show that, in patients receiving Leqembi treatment,ApoE ε4ARIA-E occurred in 8.9% of non-carriers or heterozygous patients, compared to 12.6% across all patients; similarly, ARIA-H was observed in 12.9% of these patients, versus 16.9% in the broader population.In patients receiving placebo, the incidence rates of ARIA-E and ARIA-H in this patient subgroup were 1.3% and 6.8%, respectively.

Leqembi has currently been approved in the United States, Japan, China, South Korea, Israel, the United Arab Emirates, and the United Kingdom. Eisai has also submitted regulatory applications for Leqembi in 10 countries and regions, including the European Union (EU). In June 2024, the U.S. FDA accepted Eisai's supplemental Biologics License Application (sBLA) for Leqembi’s monthly intravenous maintenance dosing, with a PDUFA target date of January 25, 2025. Earlier this month,Eisai has completed submission to the U.S. FDARolling SubmissionBLA for Leqembi Subcutaneous Autoinjector for Weekly Maintenance Dose TreatmentIf approved, the Leqembi auto-injector will be availableADThe entire injection process takes an average of only about 15 seconds when used by patients in medical institutions or at home.

Leqembi can specifically bind to soluble oligomers of β-amyloid protein.In the brains of AD patients, elevated levels of β-amyloid lead to their aggregation from monomers into dimers and soluble oligomers, which eventually further accumulate into amyloid plaques in the brain. Scientific research indicates that soluble oligomers of β-amyloid exhibit stronger cytotoxicity than monomers. Leqembi neutralizes and clears these toxic soluble oligomers by binding to them.

References:

[1] Eisai Receives Positive Opinion from the CHMP in the European Union for Lecanemab in Early Alzheimer’s Disease. Retrieved November 15, 2024 from https://www.globenewswire.com/news-release/2024/11/14/2981433/0/en/Eisai-Receives-Positive-Opinion-from-the-CHMP-in-the-European-Union-for-Lecanemab-in-Early-Alzheimer-s-Disease.html

[2] Leqembi recommended for treatment of early Alzheimer’s disease. Retrieved November 15, 2024 from https://www.ema.europa.eu/en/news/leqembi-recommended-treatment-early-alzheimers-disease

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