This is a setback for the new generation of treatments for Alzheimer's disease. The European Medicines Agency (EMA) has issued an unfavorable opinion for the marketing of the first treatment capable of reducing cognitive decline in Alzheimer's patients. This treatment, Leqembi, marketed by Biogen and Esai, was approved in the United States in 2023. However, the European Medicines Agency believes that the risks associated with taking this new treatment do not outweigh its positive effects. Explanations.
Read alsoAlzheimer's: drugs of hope
A disease that sets in silently very early
Alzheimer's disease is still poorly understood. Research suggests that it stems from a multitude of factors, including age and genetics, and the two measurable factors to date are the presence of beta-amyloid plaques and tau proteins in the brain. The accumulation of beta-amyloid protein in the form of plaques in the brain destroys neurons. In parallel, the tau protein acts, which also accumulates and fibrillates (" Tournicote") around neurons until they stop functioning properly.
This is how the memory loss and cognitive symptoms characteristic of the disease appear. In patients, beta-amyloid plaque and tau protein begin to appear silently very early in the brain, about 15 years before the first cognitive symptoms appear. This makes any attempt to slow the disease all the more difficult. Until now, no medication had succeeded in improving the clinical condition of Alzheimer's patients.
Read alsoAlzheimer's: the results of an "invaluable" study spanning more than 20 years
27% less cognitive decline
In 2023, the Food and Drug Administration (FDA), the drug regulatory authority in the United States, approved the marketing of Leqembi. Its molecule, lecanemab, has the property of binding to beta-amyloid peptides, preventing them from clumping into plaque. The result: for the first time, the reduction of plaques in the brain is accompanied by a slowing of cognitive decline.
In patients taking Leqembi, cognitive decline was 27% lower after 18 months of treatment compared to placebo. Conceptually, this is a significant advance. It validates the hypothesis that there is indeed a relationship between the presence of plaque in the brain and the onset of symptoms." , previously explained to Science and Future Professor Bruno Dubois, professor of neurology and director of the Institute of Memory and Alzheimer's Disease (IM2A) at the Pitie-Salpetriere Hospital in Paris. He emphasizes, however, " a modest effect: the disease still worsens, but less than without medication. Families and patients should know this so as not to be disappointed.. »
This proven, but weak, positive effect does not outweigh the drug's adverse effects, according to the European Medicines Agency. Indeed, the results of trials with lecanemab have shown that the drug is not without risks. Approximately 30% of the patients experienced side effects. They were severe for 10% of them, and 5% even had to stop treatment. These effects, all of the same nature, are called ARIA, amyloid-related imaging abnormalities: brain edema or hemorrhage visible on MRI. This is an inflammatory reaction, which in both cases leads to compression of the skull. Three people in the cohort are deceased because of these side effects.
"Serious side effects"
“ The committee considered that the observed effect on slowing cognitive decline does not outweigh the risk of serious side effects associated with this medicine, in particular the frequent occurrence of ARIA including brain swelling and bleeding in patients taking Leqembi.", explains the European Medicines Agency in its press release. While the majority of effects are limited to small cerebral hemorrhages, " Some patients have had serious effects, including major brain bleeding requiring hospitalization.“
It remains to be seen whether this decision will set a precedent for future drugs of the same generation to seek marketing authorization in Europe. Leqembi is not the only drug of this new generation. Donanemab (marketed under the name Kisunla) and developed by the Eli-Lilly laboratory has also shown encouraging results. Despite its side effects, the FDA has voted for its commercialization in the United States in early July 2024.
English 
French