A major Cochrane review recently cast doubt on the safety and effectiveness of amyloid-targeting Alzheimer’s drugs, although some experts and drugmakers have disputed the researchers’ conclusions.
These types of monoclonal antibodies are designed to reduce or remove amyloid-beta, a naturally occurring protein that can accumulate into sticky plaques in the brains of people with Alzheimer’s disease.
In the review, researchers analyzed results from 17 clinical trials involving 20,342 participants who had mild cognitive impairment or early-stage Alzheimer’s dementia, according to a press release.
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While previous studies have suggested that amyloid-targeting drugs can help slow disease progression, the Cochrane review found that their impact on memory decline and dementia severity was “either nonexistent or extremely small.”
“Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients,” said lead author Francesco Nonino, neurologist and epidemiologist at the IRCCS Institute of Neurological Sciences of Bologna, Italy, in the release.
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“There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect,” he went on. “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 also identified some potential safety concerns linked to the anti-amyloid drugs, including a higher likelihood of swelling and bleeding in the brain.
In many cases, these changes were detectable only on brain scans and did not cause clear symptoms, they stated. However, the long-term effects are unknown, as symptom reporting was inconsistent across studies.
Based on these findings, the researchers concluded that lowering amyloid-beta alone is unlikely to produce meaningful clinical gains. While these drugs effectively reduce amyloid levels in the brain, this change does not appear to result in improved outcomes for patients, they said.
The team recommended that future research should explore other “biological pathways” involved in Alzheimer’s disease.
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“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.”
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“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 reached out to the study authors for comment.
The Alzheimer’s Association has requested that Cochrane withdraw the analysis, calling it “scientifically flawed” and warning that it could lead to “misguided and potentially harmful conclusions.” The Cochrane analysis is lacking patients’ perspectives, according to the association.
“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 group said in a statement provided to Fox News Digital.
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The association also pointed to real-world clinical settings where amyloid-targeting monoclonal antibodies have shown efficacy and safety very similar to what was reported in the phase 3 clinical trials — “clinically meaningful slowing of disease progression/cognitive decline with modest side effects.”
“Real-world data, along with clinical trial results, should guide decision-making,” the group added.
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Lilly, maker of donanemab (Kisunla), agreed with the Alzheimer’s Association that the Cochrane review is built on an “inherently flawed methodology.”
“It pools data from across multiple amyloid-targeting therapies as a class, including molecules that did not achieve their clinical trial endpoints and were never granted regulatory approval,” a Lilly spokesperson told Fox News Digital.
“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.”
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Lilly noted that regulatory authorities around the world have evaluated donanemab’s clinical data “on its own merits,” which is the “appropriate standard for determining benefit and risk for patients.”
Eisai’s, which makes the Alzheimer’s drug lecanemab (Leqembi), echoed these 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.”
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The researchers acknowledged limitations of the study, including that clinical benefits may differ among subgroups and individual drugs. For some of the studies, follow-up periods may have been too short to detect long-term outcomes, they noted.
There was also variability between trials in terms of dosing and outcomes. Additionally, most of the trials focused on early-stage Alzheimer’s disease, which may not always apply to those with advanced disease.
