November 1901: Auguste Deter, a 51-year-old woman, was admitted to the Frankfurt asylum, disoriented, confused, with memory, language and behavioral problems. Alois Alzheimer, the psychiatrist in charge of the patient, then made the first description of the disease that bears his name – which has since become the dread of aging populations.
November 2024: the European Medicines Agency, after opposing it in July, authorizes a new drug against Alzheimer’s disease, Leqembi – a decision welcomed by patient associations, whose hope must however be tempered. This new molecule does not cure the disease, but would slow down its progression a little at an early stage. The impact would be moderate, but not zero, accompanied by side effects, at a high cost. If the drug is not yet available in France, experts are already arguing over its real benefit.
On a clinical level, Alzheimer’s disease begins with mild memory problems which progress to loss of autonomy. On a biological level, so-called protein deposits “amyloids”among others, accumulate in the brain, with progressive destruction of neurons. This treatment relies on antibodies that attack these amyloid deposits. This is why it is intended for the early stages of the disease: when it has progressed, the damage to the neurons makes any treatment useless.
Side effects
What exactly do we know about the effectiveness of Leqembi, developed by the Eisai (Japanese) and Biogen (American) laboratories? The available data is based on a unique global trial, published in 2022, involving 1,795 people aged 50 to 90 with early Alzheimer’s. Half received Leqembi infusions in hospital every two weeks, the other half only had a placebo. Efficiency, assessed by tests of memory, language and comprehension, was compiled on a scale – called « Clinical Dementia Rating » – ranging from 0 to 18, the most severe stage of dementia. At the start, the average patient score was 3.2.
After eighteen months, it reached 4.42 with treatment, 4.95 without. “It slows the progression of the disease by 27%. It’s not random, but it’s not miraculous either.says Doctor Nicolas Villain, neurologist at the Pitié-Salpêtrière hospital in Paris. The problem is that the trial only lasted eighteen months. We don’t know what happens next. Does the effect fade or last? No information to know today. » Furthermore, the drug was less effective in women and people with genetic risk factors for Alzheimer’s.
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In addition to this modest benefit, European procrastination also concerns side effects which affect 26.4% of patients, including 12.6% cerebral edema or hemorrhage. “To reduce this risk, the European Medicines Agency has asked to exclude people at risk for these complications”adds Nicolas Villain. “Of course there are risks, underlines Philippe Amouyel, professor of public health at Lille University Hospital. But the drug will be limited to patients for whom the benefits will outweigh the risks. » In France, some two million people have an early stage of the disease, but only 10 to 15% of them could receive Leqembi.
The debate also concerns the high price of the drug. It has not yet been set in France but should be close to that of the United States: $26,000 per patient per year. Sum to which must be added the cost of tests to eliminate patients at risk of complications, that of infusion placements in hospital and that of monitoring the drug by MRI, on at least four occasions… “ This medico-economic question is not negligible insofar as there are uncertainties about the long-term gainadds Nicolas Villain. That said, even a reduction that could be described as modest – 5 to 10% of admissions to nursing homes or emergencies for confusion – would represent a significant saving for the community. But today, these projections remain speculative. »
180 therapeutic trials in progress
Despite these reservations, there is great hope for one reason: the patients receiving treatment had significantly fewer amyloid plaques in the brain than the others. “These drugs reduce the amyloid load, that’s certain, specifies Doctor Carole Dufouil, Inserm researcher in Bordeaux. But in terms of clinical improvement, the effect compared to placebo is weak, even if it is statistically significant. We give a lot of hope, but our role as scientists is to base ourselves on the evidence and not to oversell the results in favor of a treatment. »
How can we understand that this drug reduces plaques in the brain, while having a very moderate effect on the disease? Alexander Caleb, professor of public health at Johns Hopkins Hospital (Maryland) explains: “It’s a problematic drug. Not surprisingly, it is not widely used in the United States. Its basic principle is to consider amyloid as a causal factor in Alzheimer’s disease, but this hypothesis is questioned by many experts. »
Can we hope for a truly curative drug? And when? “Alzheimer’s disease is complex, replies Nicolas Villain. It is the combination of drugs, as in cancer, which could ultimately have a significant effect. » Research against Alzheimer’s, long at half mast, has regained color: 180 therapeutic trials are underway around the world. “One thing is certain, concludes Professor Amouyel. The arrival of this drug puts the laboratories back in the race. This is very important for the future. »
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