Investigational Vaccine Produces Potent Antibody Response to Phosphorylated Tau in Individuals with Alzheimer Disease 

In a phase 1b/2a clinical trial (NCT04445831), an investigational antiphosphorylated-tau (antip-tau) vaccine (ACI-35.030; AC Immune SA, Lausanne, Switzerland) was evaluated. High titers of antigen-specific antibodies at potentially therapeutic levels were shown in individuals age 50 to 75 with early Alzheimer disease (AD) who received the vaccine. 
Interim data from the phase 1b/2a study showed

• The antitau IgG response targeted p-tau in all participants in the study
• 100% of participants demonstrated an antip-tau IgG response after the first injection
• Following the injection was a very high antip-tau IgG titers
• All participants elicited an antip-tau IgM response
• The vaccine was safe and well tolerated 

These results provide clinical evidence that the vaccine improves antibody responses in people over age 50 who may have attenuated immune systems. Of note, this vaccination generated antibody responses that differ substantially from the antitau monoclonal antibody semorinemab. 

Andrea Pfeifer, chief executive officer of AC Immune SA, commented, “These remarkable data show that ACI-35.030 is capable of generating unprecedented antibody responses against p-tau in an elderly population, with very high antigen-specific titers. Importantly, it generated a much stronger antibody response compared to direct injection of exogenous antibodies. As pathological p-tau is present as a precursor many years before tau accumulation in the brain is detectable via brain imaging, such results highlight the significant promise of ACI-35.030 as an early intervention for AD, especially when combined with cutting-edge p-tau diagnostics that would enable identification of people at risk of developing tau-driven disease. We look forward to continuing to advance ACI-35.030 in our collaboration with Janssen Pharmaceuticals, as we aim to bring this potentially breakthrough vaccine to patients.”

No clinically relevant adverse events were observed.