AAIC 2022 | Optimized anti-Aβ vaccination enters clinical trials in Alzheimer’s disease

Johannes Streffer, MD, AC Immune SA, Lausanne, Switzerland, discusses the clinical development of an anti-amyloid beta (Aβ) vaccine for the treatment of sporadic Alzheimer’s disease (AD) and AD in Down syndrome. Optimized ACI-24 (ACI-24.060) is a liposomal vaccine targeting Aβ for the treatment and prevention of AD. Studies investigating the original ACI-24 showed low antibody titers and no change on amyloid-PET. The optimized formulation incorporates an additional universal T-helper cell peptide, aiming to increase antibody production against pathological Aβ species. Preclinical tests of ACI-24.060 have shown the vaccination to result in the production of antibodies against Abeta1-42, pyroGlu-Aβ, and oligomers. Antibody production with a broader N-terminal Aβ sequence recognition was seen and the polyclonal antibody response was observed to mature over time. PyroGlu-Aβ is highly amyloidogenic and toxic and thus, the high titers of Ig reactive to this form of Aβ is a promising finding. A planned double-blind, placebo-controlled study (ABATE) will assess the safety, tolerability, immunogenicity and pharmacodynamic effects of ACI-24.060 in sporadic AD and people with Down syndrome. The biomarker-based design will use amyloid-PET for patient selection and response monitoring. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.