It's one of the major medical controversies of the moment: two new drugs, Leqembi and Kisunla, promise to slow Alzheimer's disease. For their advocates, it's an unprecedented opportunity. For others, it's yet another disappointment after decades of fruitless research.
"We have reached a turning point" thanks to these treatments, biologist John Hardy, whose work has guided the bulk of anti-Alzheimer's research since the 1990s, told AFP.
"We are raising unrealistic false hopes among Alzheimer's patients and their families," says British psychiatrist Rob Howard, a specialist in old age at University College London.
These statements summarize the often-contradictory positions on two recently introduced drugs for Alzheimer's disease, the most common form of dementia, with tens of millions of sufferers worldwide.
These are Leqembi, based on the molecule lecanemab and developed by the laboratories Biogen and Eisai, and Kisunla, based on donanemab from Eli Lilly, both having very similar profiles.
Far beyond expert debates, the controversy now has concrete consequences because it translates into different policies from one country to another.
While the United States successively approved lecanemab and then donanemab, the European Union (EU) refused to give the green light to the former this summer, a decision that bodes ill for the latter. In late August, the United Kingdom took a middle path by approving lecanemab but rejecting its reimbursement.
The controversy can be summed up in one sentence: Leqembi and Kisunla are undoubtedly the most effective drugs ever seen against Alzheimer's, but this effectiveness is very limited.
These treatments appear to reduce cognitive decline in patients at the onset of the disease by approximately 30%. This figure may seem high, but it represents only a small difference over the year and a half period during which the laboratory studies were conducted.
"The benefits are so small that they are almost invisible in an individual patient," Howard said.
– Astronomical cost –
Critics of these treatments say this is too little for too many risks, since these drugs sometimes cause cerebral edemas that can be fatal in rare cases.
Finally, they point to an astronomical cost. According to a study published in 2023 by the Lancet Regional Health, at the price charged by Biogen/Eisai in the United States, lecanemab, if given to all eligible patients, would represent a cost of €133 billion in the EU, an unaffordable level for healthcare systems.
Proponents of these treatments, including many neurologists, believe they can give patients precious months of autonomy. Above all, they believe they could be even more effective if administered even earlier, as research is making great strides toward early diagnosis of the disease.
And, beyond the medical debate, they accuse the EU and the United Kingdom of contributing to health inequalities: "the richest patients will go to the United States," warns Mr. Hardy.
The different camps largely correspond to the supporters and opponents of the main hypothesis regarding the mechanisms of the disease, that of the amyloid cascade, described in 1992 by Mr. Hardy in a seminal article.
She argues that the presence of amyloid protein plaques, a constant in the brains of patients, is not just one element among others, but the factor that triggers the rest of the disease. However, like most drugs developed over the decades, Leqembi and Kisunla target these amyloid plaques.
This context partly explains the virulence of some detractors, who remember how many previous treatments were defended, despite their obvious ineffectiveness, by doctors and associations. In France, several of these were finally delisted in 2018.
– Pressure from families –
"Why did learned societies support drugs that have no benefit?" pharmacist Christian Guy-Coichard, head of Formindep, an organization that monitors conflicts of interest, asked AFP. He sees this as excessive proximity between researchers, associations, and pharmaceutical groups.
Asked by AFP, the main French association, France Alzheimer, insisted on the very small proportion of its funding coming directly from Biogen/Eisai or Eli Lilly, and instead mentioned pressure from families.
"They don't understand (the EU's decision), they say to us: 'But have you reacted?'" explains Benoit Durand, deputy director of the association, also fearing that laboratories will lose interest in anti-Alzheimer's research.
However, even within the pharmaceutical industry, some players admit that past experience doesn't necessarily inspire confidence. A doctor who works for Eli Lilly criticizes Biogen for overselling a previous treatment, Aduhelm, which was controversially approved in the United States in 2021 before being withdrawn from the market.
"Aduhelm's studies were really not clean... Biogen did everything wrong: it caused a lot of harm and sowed chaos in the discipline," laments this source, speaking on condition of anonymity. Interviewed by AFP, Biogen said it complied "with the principles of scientific research as well as legal and regulatory requirements."
But the Eli Lilly doctor calls for looking to the future rather than the past, defending the value of new treatments. Nevertheless, like many specialists, he admits that mechanisms other than amyloid must be explored.
"Given the complexity of Alzheimer's disease, it is unlikely that treatments (following this path) could achieve more pronounced effects" than Leqembi and Kisunla, concluded in August in the Journal of Prevention of Alzheimer's Disease, a consensus signed by many experts on the disease, judging however that the new drugs mark "a crucial step".
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