Pharmacy Daily | Death knell for anti-amyloids?

ANTI-AMYLOID drugs for Alzheimer's disease are unlikely to have any clinically meaningful benefits, but may increase the risk of bleeding and swelling in the brain, according to a new Cochrane review published today.

The drugs - such as aducanumab, lecanemab, and donanemab - were developed to help remove the protein amyloid beta from the brains of people with early Alzheimer's disease in the hope of preventing or slowing disease progression.

The review examined data from 17 clinical trials including over 20,000 participants, all looking at the impact of anti-amyloid drugs on people with mild cognitive impairment or mild dementia due to Alzheimer's disease.

The research found that while early trials showed promising results, further analysis showed this did not translate into meaningful change for patients, with effects on cognitive decline and dementia severity falling well below established thresholds for the minimum clinically important difference.

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

"There is now a convincing body of evidence converging on the conclusion that there is no clinically meaningful effect.

"While early trials showed results that were statistically significant, it is important to distinguish between this and clinical relevance."

In addition to the absence of clinically meaningful effects, the review found that anti-amyloid drugs likely increase the risk of swelling and bleeding in the brain.

This was observed in brain scans without any apparent symptoms for most patients, although any long-term effects remain unclear since reporting of symptoms was inconsistent across trials.

The authors noted that while the drugs do successfully remove amyloid proteins from the brain, the evidence suggested that future trials targeting amyloid beta removal are unlikely to provide clear benefit to patients.

They recommended that future research on Alzheimer's treatment should focus on other mechanisms.

"This review does not prove amyloid has no role in Alzheimer's, and it does not rule out future amyloid-directed therapies that may yet help patients," commented Professor Bryce Vissel from the Faculty of Medicine at UNSW.

"But it does show that the current generation of anti-amyloid drugs is not delivering the promise that has surrounded it."

Australia recently approved lecanemab and donanemab for treatment in early Alzheimer's disease, although applications for listing on the PBS were not recommended by the Pharmaceutical Benefits Advisory Committee due to the small potential benefits set against high burden to patients and costs to the health system.

Read the study HERE. KB