Clinical efficacy and controversies of aducanumab

Abstract

The anti-amyloid monoclonal antibody aducanumab has been approved by FDA in Jun 2021. It is the first diseasemodifying drug for the treatment of mild Alzheimer’s Disease (AD) to improve cognitive functions by clearing the amyloid plaques in brain. This review discussed all aspects of the aducanumab development, including the structural and kinetic perspective in its discovery, the most important results from phase 1 and two phase 3 clinical trials and its controversies. Despite FDA approval, aducanumab did not announce a success in controlling the development of AD at early-stages possibly due to the contribution from other confounding pathological pathways and mixed biomarkers occurred during AD pathogenesis. Thereby, it is vital to conduct long-term post-market surveillance, as well as concentrating more on researching AD pathogenesis. Other potential therapeutic targets, such as inhibiting unfolded protein response (UPR) signaling pathways, might also contribute to the progression of AD and therefore catch increasing attention in research field.