Anti-Amyloid Monoclonal Antibody (MAB) Therapy for Alzheimer’s Disease

Anti-amyloid monoclonal antibodies (MAB’s) are approved by the U.S. Food and Drug Administration as disease targeted therapies (DTTs) for the treatment of early Alzheimer’s disease.  They are noted to change a defining feature of Alzheimer’s disease, the presence of amyloid plaques.  Use of anti-amyloid MABs requires the early detection of Alzheimer’s disease, the use of biomarkers to diagnose Alzheimer’s disease, and adjustments of healthcare systems to ensure safe delivery of these therapies.  In the U.S., MABs that currently have FDA approval as of the writing of this post are Aducanumab (now discontinued), Lecanemab, and Donanemab, and new anti-amyloid MABS are being developed.

Anti-amyloid MABS do not arrest or reverse Alzheimer’s disease, but have been shown to slow clinical decline, and offer those with Azheimer’s disease the opportunity to function at a higher level for a longer period of time ⁽¹⁾.  Eligible patients experience approximately 30% reduction in the rate of loss of cognition and function.  In 18-month clinical trials, this 30% slowing translated to approximately a five-month delay in disease milestones, and longer periods of treatment are expected to produce greater clinical benefits.  Adverse events include reactions to intravenous infusions, and amyloid-related imaging abnormalities (ARIA; usually asymptomatic, but can have serious health consequences and must be carefully managed). 

Patient selection for anti-amyloid MABs is critical for its success ⁽¹⁾.  This includes baseline MRI, determination of amyloid status (elevated beta-amyloid, via PET scan or cerebrospinal fluid analysis), diagnosis of Mild Cognitive Impairment or mild dementia due to Alzheimer’s ⁽²⁾, and identification of patients who can successfully adhere to the treatment regimen.  Anti-amyloid MABS are administered once or twice per month, and infusion resources are required for anti-amyloid MABs to be administered.  Treatment includes regular MRI scans to monitor for side effects (ARIA).    Anti-amyloid MABS may contribute to precision-based patient selection, and combination treatment regimens for Alzheimer’s disease in the future as additional treatment options become available ⁽²⁾.   

References:

1. https://www.sciencedirect.com/science/article/pii/S1878747925000480#:~:text=Anti%2Damyloid%20monoclonal%20antibodies%20(MABs)%20are%20the%20first%20agents,safe%20delivery%20of%20these%20therapies.
2. https://www.neurology.org/doi/10.1212/WNL.0000000000207757#:~:text=Abstract,care%20partners%20on%20potential%20benefits.