The CHMP Issues a Negative Opinion for the Approval of Leqembi in Europe

On July 25, 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a negative opinion for Leqembi (lecanemab-irmb; Eisai, Tokyo, Japan; Biogen, Cambridge, MA), recommending that the European Commission refuse the medication’s marketing authorization application. The granting of marketing authorization provides approval to market a medicine within European Union (EU) member states. From the date of the decision, Eisai has 15 days to request re-examination.

The CHMP’s negative opinion was based on an analysis of the cost-benefit relationship of treating people with Alzheimer disease (AD) using Leqembi. According to the CHMP, the difference in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores between participants treated with Leqembi and those treated with placebo during the phase 3 Clarity AD clinical trial (NCT03887455) was not significant enough to justify the medication’s use, in consideration of associated serious adverse events (SAEs). Amyloid-related imaging abnormalities (ARIA) were cited as the most significant of these SAEs, a complication resulting from treatment with some disease-modifying therapies (DMTs). People with the apolipoprotein E ε4 (APOE ε4) genotype are at higher risk of developing ARIA.

In the decision, the CHMP explains “Although most cases of ARIA in the main study were not serious and did not involve symptoms, some patients had serious events, including large bleeds in the brain which required hospitalisation. The seriousness of this side effect should be considered in the context of the small effect seen with the medicine.”

Eisai (Tokyo, Japan) and Biogen (Cambridge, Massachusetts) have expressed an intention to seek re-examination in response to the CHMP’s negative opinion for marketing authorization for Leqembi. Lynn Kramer, MD, Chief Clinical Officer at Eisai, said, “We are extremely disappointed by the CHMP’s negative opinion and understand that this may also be disappointing for the wider Alzheimer’s disease (AD) community. AD is an irreversible, neurodegenerative disease that poses significant challenges to those living with AD, their care partners and society.”

Leqembi was approved by the Food and Drug Administration (FDA) in July 2024 for subcutaneous infusion for the treatment of people with Alzheimer disease, and the medication’s label contains a Boxed Warning for ARIA.