Bapineuzumab and solanezumab for Alzheimer's disease: is the 'amyloid cascade hypothesis' still alive?

• Published in: Expert opinion on biological therapy Vol. 13; no. 7; p. 1075
• Main Authors: Tayeb, Haythum O, Murray, Evan D, Price, Bruce H, Tarazi, Frank I
• Format: Journal Article
• Language: English
• Published: England 01.07.2013
• Subjects: Alzheimer Disease - immunology; Alzheimer Disease - therapy; Animals; Antibodies, Monoclonal, Humanized - therapeutic use; Humans; Immunotherapy
• ISSN: 1744-7682
• DOI: 10.1517/14712598.2013.789856

The 'amyloid cascade hypothesis' remains the leading hypothesis to explain the pathophysiology of Alzheimer's disease (AD). Immunotherapeutic agents have been developed to remove the neurotoxic amyloid β42 protein and prevent the hypothesized amyloid β42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab. This article briefly reviews the experimental agents in development for treatment of AD and then discusses the results of bapineuzumab and solanezumab in AD patients, as reported in preclinical studies, clinical trials and press releases. Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, analysis of pooled data from both trials showed a significant reduction in cognitive decline in mild AD patients. The improvement was associated with an increase in plasma amyloid-β (Aβ) levels and a low incidence of ARIA in solanezumab-treated patients. The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the 'amyloid cascade hypothesis' of AD.