Cochrane Review Finds Little Benefit from Amyloid-Targeting Alzheimer's Drugs

A major Cochrane review has questioned the safety and effectiveness of amyloid-targeting Alzheimer's drugs. Some experts and drugmakers have challenged the researchers' conclusions.

These monoclonal antibodies aim to reduce or remove amyloid-beta, a protein that forms sticky plaques in the brains of Alzheimer's patients.

The review examined results from 17 clinical trials with 20,342 participants who had mild cognitive impairment or early-stage Alzheimer's dementia, according to a press release.

Previous studies indicated these drugs slow disease progression. But the Cochrane review concluded their effects on memory decline and dementia severity were either nonexistent or extremely small.

"Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients," said lead author Francesco Nonino, a neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna, Italy, in the release.

"There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect," he added. "While early trials showed results that were statistically significant, it is important to distinguish between this and clinical relevance. It is common for trials to find statistically significant results that do not translate into a meaningful clinical difference for patients."

The researchers noted potential safety issues with the drugs, such as increased risks of brain swelling and bleeding. In many cases, these changes appeared only on brain scans without clear symptoms. Long-term effects remain unknown due to inconsistent symptom reporting across studies.

The team said lowering amyloid-beta alone is unlikely to yield meaningful clinical gains. The drugs do reduce amyloid levels in the brain, but this does not improve patient outcomes.

"Real-world data, along with clinical trial results, should guide decision-making."

They recommended future research into other biological pathways in Alzheimer's disease.

"I see Alzheimer's patients in my clinic every week and I wish I had an effective treatment to offer them," said senior author Edo Richard, professor of neurology at Radboud University Medical Centre, in the release. "Existing approved drugs offer some benefit for some patients, but there remains a high unmet need for more effective treatments."

"Given the absence of correlation between amyloid removal and clinical benefit, we need to explore other pathways to help address this devastating disease."

Fox News Digital contacted the study authors for comment.

The Alzheimer's Association called for Cochrane to withdraw the analysis, labeling it scientifically flawed and warning of misguided conclusions. The review lacks patients' perspectives, the group said.

"Many people living with mild cognitive impairment and mild dementia due to Alzheimer’s disease who are using these treatments are taking trips they weren’t sure they’d take, spending joyful time with friends and family, making plans for next month, doing things they love, and staying present in their lives and the lives of the people they care about," the association said in a statement to Fox News Digital.

The group cited real-world settings where the drugs showed efficacy and safety matching phase 3 trials, with clinically meaningful slowing of cognitive decline and modest side effects.

"Real-world data, along with clinical trial results, should guide decision-making," it added.

Lilly, maker of donanemab (Kisunla), said the review used an inherently flawed methodology by pooling data from multiple amyloid-targeting therapies, including unapproved ones.

"Combining data on unsuccessful molecules with approved medicines artificially dilutes the observed benefit and produces class-level conclusions that do not reflect the evidence for any individual approved therapy," a Lilly spokesperson told Fox News Digital.

Lilly said regulators worldwide evaluated donanemab on its own merits.

Eisai, maker of lecanemab (Leqembi), raised similar concerns.

"The U.S. Food and Drug Administration has stated that lecanemab is part of a newer generation of anti-amyloid therapies targeting aggregated amyloid and has learned from previous failures," an Eisai spokesperson told Fox News Digital.

"Extensive long-term clinical data out to four years and real-world experience with tens of thousands of patients globally show that patients who receive lecanemab continue to benefit from treatment."

The researchers acknowledged study limitations, including possible differences in benefits across subgroups and drugs. Some trials had short follow-up periods. Dosing and outcomes varied, and most focused on early-stage disease.