Decades of studies have investigated Alzheimer’s disease therapeutics targeted against amyloid beta (Aβ), hoping to prevent or slow cognitive decline. Prior to the approval of anti-Aβ monoclonal antibody aducanumab, very little success was achieved through this approach. Johannes Streffer, MD, AC Immune SA, Lausanne, Switzerland, shares insights on what we have learned from attempts so far and if amyloid lowering is still a valuable approach. Dr Streffer comments that several lines of accumulating evidence suggest decreasing amyloid plaque formation is of clinical value, but several important factors must be considered. For example, drug exposure has been shown to have a significant effect. In the pivotal ENGAGE and EMERGE trials, aducanumab was shown to dose-dependently reduce amyloid deposition and measures of cognitive decline. The slowing of progression noted was much lower in the low-dose group compared to those receiving a high dose. Additionally, trials of donanemab have shown the importance of treating patients early in the course of disease. Finally, Dr Streffer emphasizes that an anti-amyloid approach alone is unlikely to be sufficient, but that combinatory therapy with other targeted agents may be more valuable in the future. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.
