Anti-amyloid drugs

Anti-amyloid drugs, also known as anti-amyloid antibodies (AAA), are a class of monoclonal antibodies developed to treat Alzheimer's disease. The first drug in the class to be developed, in the early 2000s, is bapineuzumab, but it did not show effectiveness in later-stage trials. The first drug to be approved by the US Food and Drug Administration (FDA) is aducanumab—in 2021.

Approved drugs
As of 2022, none of these drugs has been approved by the European Medicines Agency.

Efficacy
A 2023 review found that "Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety." A 2022 review finds "a statistically significant but slight clinical effect of these drugs emerges in patients with early AD after 18 months" and states, "The risk/benefit ratio of this class of drugs in early AD remains so far questionable after 18 months."

From a 2023 statement by the European Association of Neurology and the European Psychiatric Association, "Anti-Aβ antibodies represent a significant advance in the treatment of AD, but their effectiveness is moderate and much work remains to be done to improve their efficacy, safety and accessibility."

In a 2023 commentary, the authors express concern that the results of the trials, which are based on scoring by patients and their caregivers, of these drugs could be confounded by unblinding produced by adverse effects. They also support running studies designed to distinguish between disease-modifying and symptomatic effects.

Amyloid related imaging abnormalities
Amyloid-related imaging abnormalities are a relatively uncommon but serious adverse effect.

Accelerated brain volume loss
Brain volume loss is a symptom of Alzheimer's disease and is accelerated by anti-amyloid drugs developed to treat it. One meta-analysis found that people with mild cognitive impairment treated with anti-amyloid drugs would reach the brain volume associated with full Alzheimer's disease eight months earlier than those who received no such treatment. The significance of the brain volume loss caused by these drugs is unknown.

The mechanism is not understood. Amyloid-related imaging abnormalities (ARIA) have been suggested as a possible cause of the accelerated brain volume loss. Others say it may be attributed to the reduction in amyloid plaques.

Accelerated brain volume loss has been reported with lecanemab, aducanumab, donanemab, and other anti-amyloid drugs. Hippocampal, ventricular, and whole brain volumes are reported in studies and declines in all three have been found. However, the affected parts of the brain are not fully understood.

Drug development
The approved anti-amyloid drugs were developed after years of unsuccessful attempts to develop a disease-modifying treatment for Alzheimer's disease.

Cost
Concerns have been raised about the high cost of the drugs and accessibility to patients.