Alzheimer’s: Europe blocks highly anticipated treatment authorized in the USA

On July 26, theEuropean Medicines Agency (EMA) has refused to market Leqembi (lecanemab) for the treatment of early-stage Alzheimer’s disease in Europe. On 3 July, the US authorities had given the green light for the drug to be marketed. How can such a difference in assessment be explained?

A drug that targets amyloid plaques

Leqembi is a drug designed to target amyloid plaques in the brain, a key pathological hallmark of Alzheimer’s disease. Clinical trials had shown promising results, suggesting that Leqembi could slow cognitive decline in patients at an early stage of the disease.

In July 2023, Eli Lilly released the results of its phase 3 trial, revealing a dramatic 84% reduction in amyloid burden after 18 months of treatment. In addition, patients showed a 35% slowing of cognitive and functional decline and a 39% reduction in the risk of progression to a more advanced clinical stage of the disease. Finally, patients who had sufficiently low levels of amyloid deposits were able to stop treatment.

The 3 reasons for the refusal of the European Medicines Agency

But The European authorities have justified their refusal to market of this medicine for three main reasons:

• A small effect on the score of cognitive ability assessment tests: The main study showed that after 18 months of treatment, the CDR-SB score (which measures the level of cognitive impairment and its impact on daily life) of patients treated with Leqembi had increased by 1.21 compared to 1.66 in those who received the placebo. A difference considered “small” by the EMEA, and therefore a “observed effect of Leqembi on delaying cognitive decline (which) does not outweigh the risk of serious adverse events associated with the drug” ;
• Potentially serious side effects: The risk highlighted by the EMEA is “the frequent occurrence of amyloid-related imaging abnormalities (ARIA), a side effect seen on brain imaging that results in swelling and potential bleeding 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 major bleeding in the brain that required hospitalization” ;
• A higher risk of complications for certain genetic forms (notably ApoE4): The risk of ARIA is greater in people who carry a certain form of the gene that codes for the protein apolipoprotein E, called ApoE4.The risk is higher 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” specifies the press release from the European agency.

“A hard blow for patients and their families” according to France Alzheimer

France Alzheimer reacted to this announcement in a communicated : “For those affected and their loved ones, this news is particularly disappointing. The lack of new effective treatments limits the options available to slow the progression of the disease and improve the quality of life of people with Alzheimer’s. This situation is all the more discouraging given that other regions of the world, such as the United States and countries in Asian territories, already have authorizations for several of these new drugs. This decision also risks compromising the accessibility of future therapeutic treatments, making investment by manufacturers very risky in Europe.“.

In the United States, another treatment developed by Esai and Biogen, Aduhelm ® (aducanumab) had benefited from a accelerated marketing authorization in the United States in June 2021. A decision that had been criticized due to the lack of evidence of effectiveness. On December 16, 2021, the European Agency had rejected the medicine due to insufficient data.

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