Among active and passive anti-β-amyloid (Aβ) immunotherapies for Alzheimer's disease (AD), bapineuzumab and solanezumab, two humanized monoclonal antibodies, failed to show significant clinical benefits in mild-to-moderate AD patients in large Phase III clinical trials. Another ongoing Phase III trial of solanezumab aims to confirm positive findings in mild AD patients. Gantenerumab is the first fully human anti-Aβ monoclonal antibody directed to both N-terminal and central regions of Aβ. A 6-month PET study in 16 AD patients showed that gantenerumab treatment dose-dependently reduced brain Aβ deposition, possibly stimulating microglial-mediated phagocytosis. Two ongoing Phase III trials of gantenerumab in patients with prodromal or mild dementia due to AD will determine if any reduction in brain Aβ levels will translate into clinical benefits. An ongoing secondary prevention trial of gantenerumab in presymptomatic subjects with genetic mutations for autosomal-dominant AD will verify the utility of anti-Aβ monoclonal antibodies as prevention therapy.
Keywords: Alzheimer’s disease; cognitive disorder; dementia; gantenerumab; monoclonal antibody; passive immunotherapy; solanezumab.