'Blockbuster' Alzheimer's drugs show no real benefit, major review finds
After years of promise, amyloid-targeting drugs may mark not a breakthrough, but a turning point toward rethinking Alzheimer's treatment strategies.
A class of drugs targeting amyloid beta proteins – long associated with Alzheimer’s disease – has been widely touted as a breakthrough in neurology. But a major new review challenges that promise.
An analysis of 17 clinical trials involving 20,342 participants finds these drugs deliver no clinically meaningful benefit. More concerning, they may raise the risk of brain swelling and bleeding, according to a landmark review published by the Cochrane Collaboration, which evaluates medical evidence.
Alzheimer’s disease remains the leading cause of dementia, typically affecting older adults, though early-onset cases in those under 65 are rising. For decades, treatment has focused on managing symptoms, with no proven way to slow or stop the disease.
Alzheimer’s accounts for 60–70 percent of dementia cases worldwide. The dominant scientific model has linked the disease to the build-up of amyloid plaques and tau tangles in the brain – changes believed to kill brain cells and shrink brain volume over time.
This understanding has driven the development of so-called disease-modifying therapies, a senior neurologist at AIIMS, New Delhi told India Today.
NEW EVIDENCE
The review evaluated seven amyloid-targeting monoclonal antibodies: aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, and solanezumab. These lab-engineered proteins are designed to bind to specific biological targets and are widely used in fields such as cancer treatment.
Across multiple randomized controlled trials, the findings show that any effects on cognitive decline or disease severity were absent or minimal—well below thresholds considered clinically meaningful.
Additionally, clinical trial results show that they can cause side effects, including brain swelling and bleeding, which can be fatal in some cases.
The drugmakers have themselves stated that these can lead to serious adverse effects, such as amyloid-related imaging abnormalities (ARIA) – a kind of brain swelling that can lead to severe symptoms – and infusion-related reactions.
“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.
He added that while some early trials showed statistically significant results, these did not translate into real-world clinical benefit.
INDIA CONTEXT
Donanemab – one of the most high-profile drugs in this class, alongside lecanemab, has been approved by India’s drug regulator, with US-based manufacturer Eli Lilly and Company planning a launch in the coming months.
India faces a growing burden as its population ages. By 2030, an estimated 8 million people in the country are expected to live with dementia, most of them with Alzheimer’s disease.
Despite successfully clearing amyloid from the brain, these drugs do not improve patient outcomes, the review finds.
Researchers conclude that future trials targeting amyloid removal are unlikely to yield meaningful benefits and recommend shifting focus to alternative biological pathways, many of which are already under investigation.