The Food and Drug Administration (FDA) has recently approved novel drugs for the treatment of Alzheimer’s disease, sparking both enthusiasm and controversy. These drugs are antibody therapies that target toxic protein aggregates in the brain. With the rapidly aging population and the prevalence of Alzheimer’s disease, there is an urgent need for disease-modifying treatments that can slow its progression.
Aducanumab was the first antibody therapy targeting amyloid-beta protein deposits to receive FDA approval in 2021. However, clinical trials showed inconsistent improvements in cognitive function, leading Biogen to suspend sales. In contrast, two other anti-amyloid antibodies, lecanemab and donanemab, have shown promise in slowing cognitive decline in individuals with early Alzheimer’s disease and received FDA approval.
The development of anti-amyloid antibody treatments is based on the amyloid cascade hypothesis, which suggests that the accumulation of beta-amyloid protein triggers changes that lead to Alzheimer’s disease. These antibodies have different affinities for various types of beta-amyloid aggregates and work by potentially activating an immune response against the aggregates to remove them.
While the approval of lecanemab and donanemab has been viewed as a breakthrough, some researchers have raised concerns about the modest clinical benefits of these therapies. Safety risks, costs, and accessibility also pose challenges. Adverse effects, such as amyloid-related imaging abnormalities (ARIA), have been observed in a significant proportion of participants in clinical trials, necessitating frequent MRI scans and clinical follow-ups.
Individuals with the APOE4 gene, which is linked to an increased risk of Alzheimer’s disease, are at higher risk of adverse effects from anti-amyloid antibody treatments. Screening and diagnosis of eligible individuals for these therapies also pose challenges, as most people with Alzheimer’s are not diagnosed until later stages of the disease. Investment in diagnostic infrastructure and workforce is necessary to ensure that eligible individuals can access these treatments in the early stages of Alzheimer’s disease.
The cost of receiving infusions of lecanemab and donanemab is significant, and additional costs for screening, diagnosis, genetic testing, and managing adverse effects need to be considered. Advances in diagnostic methods and the identification of novel biomarkers have the potential to reduce costs and improve accessibility to anti-amyloid therapies. Further research is needed to understand the long-term effects and clinical benefits of these treatments, as well as their role in combination with other therapies for Alzheimer’s disease.
