Drugs once hailed as breakthroughs in the battle against Alzheimer’s disease offer little meaningful benefit to patients, according to a major review published Thursday, though some experts have criticised the findings.
The analysis, conducted by the Cochrane organisation, widely regarded as the gold standard for evaluating medical evidence, examined treatments targeting amyloid plaques, the protein deposits that accumulate in the brains of people with Alzheimer’s.
For decades, researchers have sought to eliminate these plaques, believing they were central to the development of dementia, which affects millions of older adults worldwide.
After years of costly and largely unsuccessful trials, two anti-amyloid drugs — lecanemab and donanemab — were initially celebrated as potential gamechangers, offering hope of slowing disease progression. Both medicines have since been approved in the United States and European Union.
However, concerns about their limited effectiveness, high costs, and serious side effects including increased risks of brain swelling and bleeding have tempered enthusiasm. Public health systems in the UK and France have declined to cover the treatments.
The Cochrane review pooled data from 17 clinical trials involving more than 20,000 people with mild cognitive impairment or early-stage dementia.
Conducted over roughly 18 months, the studies assessed seven anti-amyloid drugs. Only one trial focused on donanemab, marketed as Kisunla by Eli Lilly, while another examined lecanemab, sold as Leqembi by Biogen and Eisai.
Lead author Francesco Nonino of Italy’s IRCCS institute said that while early results suggested statistically significant improvements, these did not translate into “something clinically meaningful for patients.”
Brain scans confirmed the drugs successfully removed amyloid deposits, but co-author Edo Richard of Radboud University Medical Centre in the Netherlands said, “The idea that removing amyloids will benefit patients was refuted by our results.”
Not delivering on promise
Edo Richard, who has previously voiced scepticism about anti-amyloid drugs, said he hopes future research focusing on other biological mechanisms behind Alzheimer’s will lead to more effective treatments.
British biologist John Hardy, who first proposed the amyloid hypothesis in the 1990s, criticised the Cochrane review for grouping lecanemab and donanemab together with drugs already shown to be ineffective, arguing this skewed the overall results downward. “This is a silly paper which should not have been published,” Hardy told AFP, noting he has consulted for Eli Lilly, Biogen and Eisai.
Responding to such criticism, Richard said that while the drugs may act in different ways, they all share the same target: amyloid beta proteins.
Australian neuroscientist Bryce Vissel, who was not involved in the review, added that the findings “do not prove amyloid has no role in Alzheimer’s, and they do not rule out future amyloid-directed therapies that may yet help patients.”
“But it does show that the current generation of anti-amyloid drugs is not delivering the promise that has surrounded it,” Vissel said.
