It is 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 is an unprecedented opportunity. For others, it is 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 false and unrealistic hopes among Alzheimer’s patients and their families,” says British psychiatrist Rob Howard, a specialist in old age at University College London.
The statements sum up 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 lecanemab molecule and developed by the Biogen and Eisai laboratories, and Kisunla, based on Eli Lilly’s donanemab, both of which have very similar profiles.
Far beyond the 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 this summer to give the green light to the former, a decision that bodes ill for the latter. At the end of 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 about 30%. This figure may seem high, but it represents only a small difference over the year and a half 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
For critics of these treatments, this is too little for too many risks, since these drugs sometimes cause cerebral edema which proves fatal in rare cases.
Finally, they point out an astronomical cost. According to a study published in 2023 by the Lancet Regional Health, at the price asked by Biogen/Eisai in the United States, lecanemab would represent, if given to all eligible patients, a cost of 133 billion euros in the EU, an unaffordable level for health systems.
Proponents of these treatments, including many neurologists, believe they can give patients precious months of autonomy. Above all, they believe they could be more effective if given even earlier, as research is making great strides to enable early diagnosis of the disease.
And, beyond the medical debate, they accuse the EU and the UK 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 the majority of 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 them were finally delisted in 2018.
Pressure from families
“Why did learned societies support drugs that have no interest?” asks pharmacist Christian Guy-Coichard, head of Formindep, an organization that monitors conflicts of interest, to 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 low share of its funding coming directly from Biogen/Eisai or Eli Lilly, and instead mentioned pressure from families.
“They don’t understand [la décision de l’UE]they say to us: “But did you react?”, explains Benoît Durand, deputy director of the association, also fearing that laboratories will lose interest in anti-Alzheimer’s research.
But even within the pharmaceutical industry, some players admit that the past is not necessarily a source of 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 pulled from the market.
“Aduhelm’s studies were really not clean… Biogen did everything it could: it caused a lot of harm and sowed chaos in the discipline,” regrets this source on condition of anonymity. Questioned 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 interest of new treatments. Nevertheless, like many specialists, he admits that other mechanisms than the amyloid track must be explored.
“Given the complexity of Alzheimer’s disease, it is unlikely that treatments [suivant cette piste] “may 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.”