On 25 July 2024 the European Medicines Agency (EMA) rejected a licence for lecanemab to treat Alzheimer’s disease.
The EMA said the benefits did not counterbalance the risk of serious side effects, especially bleeding and swelling in the brain.
The MHRA in the UK is still considering whether to grant a licence, and a decision is expected soon. The drug was approved in the United States earlier this year and has already been approved by regulatory authorities in China, Hong Kong, Israel, Japan and South Korea.
In trials, lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months.
Alzheimer’s researchers called the trial results “historic” because no previous drug had convincingly shown that the underlying mechanism of the disease could be slowed.
What were the main reasons for refusing the application?
The main study showed that after 18 months of treatment, the CDR-SB score in patients treated with Leqembi increased by 1.21 compared with 1.66 in those who received placebo. Although patients given Leqembi had lower CDR-SB scores than those given placebo, the difference between the two groups was small. EMA’s human medicines committee, the CHMP, considered that the observed effect of Leqembi on delaying cognitive decline does not counterbalance the risk of serious adverse events associated with the medicine.
The most important safety concern with Leqembi is the frequent occurrence of amyloid-related imaging abnormalities (ARIA), a side effect, seen in brain imaging, that involves swelling and potential bleedings in the brain. 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.
In addition, the CHMP was concerned by the fact that the risk of ARIA is more pronounced in people who have a certain form of the gene for the protein apolipoprotein E called ApoE4. The risk is highest in people with 2 copies of the ApoE4 gene, who are known to be at risk of developing Alzheimer’s disease and would therefore be likely to become eligible for treatment with Leqembi.
In reaching its opinion, the CHMP also considered the views of a scientific advisory group on neurology, which included experts such as neurologists and people living with the disease.
Overall, the CHMP considered that the benefits of treatment are not large enough to outweigh the risks associated with Leqembi. Therefore, it recommended refusing marketing authorisation in the EU.
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