Anti-Amyloid-beta monoclonal antibodies as an immunotherapy for Alzheimer’s disease was reviewed by Christopher van Dyck in the academic publication Biological Psychiatry (Biol. Psychiatry 2018 Feb 15:83(4) 311-319) back in 2018. He described the “pitfalls and promises” of several monoclonal antibodies being scrutinised for their efficacy in binding the aberrant amyloid-beta protein seen in the brains of people suffering from Alzheimer’s disease. The hypothesis being that once bound to the antibody, amyloid-beta would cease to play a role in the cognitive decline intrinsic to this neurodegenerative disease. He described the results as being “fraught with failure and confusing”. 

On 29 November 2022, CH Van Dyke and colleagues published in the The New England Journal of Medicine (DOI: 10.1056/NEJMoa 2212948) the results of an 18 month, multicentre clinical trial of the

monoclonal antibody Lecanemab, which like the others reported in the 2018 paper, binds amyloid beta.

Analysis of several hundred Alzheimer’s disease patients and controls treated with either Lecanemab or a placebo drug, demonstrated reduction in the markers for amyloid in the early Alzheimer’s disease patient group.  Patients also demonstrated moderately less decline than placebo controls when performing tests to measure cognitive performance at 18 months post drug receipt. Nevertheless, moderate benefit was associated with severe adverse effects. The authors acknowledge that trials exceeding 18 months are required to determine the efficacy and safety of Lecanemab in early Alzheimer’s disease.  In the event a license is sought for use of the drug in the UK, the Medicines and Healthcare products Regulatory Agency will need to be convinced that the benefits

significantly outweigh the risks.

Readers may recall that in 1989, the cholinesterase inhibitor, Tacrine was licensed as a treatment for Alzheimer’s disease (marketed as Cognex). The benefit was limited and the drug was withdrawn due to safety concerns.

The identification of the aberrant proteins of tau fibrillary tangles and amyloid plaques in the brains of Alzheimer’s disease patients and their role in dementia has been established for decades yet little progress has been made with developing safe and efficacious treatments. The Campaign for Alzheimer’s Research, through its funding of UK and European collaborative research platforms, facilitates translation of laboratory research into viable treatments. 

Your financial support is vital to this continued endeavour.

Sarah-Jane Richards

6 december 2022