At its meeting in July 2024, the Committee for Medicinal Products for Human Use (Committee for Medicinal Products for Human UseCHMP) of the European Medicines Agency (EMA) has recommended against granting marketing authorisation to Leqembi (lecanemab; Eisai GmbH), a medicine for the treatment of Alzheimer’s disease.
The Committee considered that the observed effect of Leqembi in delaying cognitive decline did not outweigh the risk of serious adverse effects associated with the medicine, in particular the frequent occurrence of amyloid-related imaging abnormalities (ARIA) which involve swelling and potential haemorrhage in the brain.
The CHMP stressed that the company that requested authorisation could request a review within 15 days of receipt of the opinion.
Test data
Leqembi has been developed to treat adults with mild cognitive impairment due to Alzheimer’s disease and early Alzheimer’s disease. The active substance, lecanemab, is a monoclonal antibody that binds to amyloid beta and thus aims to delay the worsening of the disease. The medicine is given as an infusion every two weeks.
In its assessment, the CHMP looked at the results of a study involving 1,795 people with early-stage Alzheimer’s disease who had beta-amyloid plaques in their brain and who received either Leqembi (n=898) or placebo (n=897).
The main measure of effectiveness was change in symptoms after 18 months, measured using the scale Clinical Dementia Rating-Sum of Boxes (CDR-SB) which is used to assess the severity of Alzheimer’s disease. This scale includes questions that help determine the extent to which the patient’s daily life has been affected by cognitive impairment and ranges from 0 to 18, with higher scores indicating greater impairment.
The mean CDR-SB score at baseline was about 3.2 in both groups. The study showed that after 18 months of treatment, the CDR-SB score of patients treated with Leqembi had increased by 1.21, compared with 1.66 for those who received placebo. Although the CDR-SB score of patients treated with Leqembi was lower than that of patients treated with placebo, the difference between the two groups was small.
The study authors concluded that lecanemab reduced amyloid markers in early Alzheimer’s disease and caused moderately less decline in measures of cognition and function than placebo at 18 months, but was associated with adverse effects.
Amyloid-related imaging abnormalities
The CHMP highlighted that the most important safety concern with Leqembi was the common occurrence of ARIA, a side effect seen on brain imaging that involves swelling and potential bleeding in the brain.
Although most cases of ARIA in the study reviewed were not serious and did not cause symptoms, some patients had serious events, including major bleeding in the brain that required hospitalisation, the CHMP said.
In addition, the EMA Committee was concerned that the risk of ARIA is greater in people who have a certain form of the apolipoprotein E (APOE4) gene. The risk is highest in people with two copies of the APOE4 gene, who are known to be at risk of developing Alzheimer’s disease and who would therefore be likely to be eligible for treatment with Leqembi. People with two copies of APOE4, known as APOE4 homozygotes, are estimated to have a 60% risk of developing Alzheimer’s-type dementia by the age of 85.
The drug was approved by the U.S. Food and Drug Administration in 2023. The U.S. agency also authorized the anti-amyloid treatment donanemab (Eli Lilly) in July 2024.
This article was translated from Medscape.com using multiple editorial tools, including AI, in the process. The content was reviewed by the editorial staff before publication.
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