Alzheimer Diseae Drug Development Shifts as Tau Antibody Research Falters

Several recent trial readouts have renewed discussion about where Alzheimer’s disease research is heading, particularly in the area of tau-targeting therapies. Multiple monoclonal antibodies directed at various tau epitopes have not shown clinical benefit in mid-stage studies, including agents from Johnson & Johnson, UCB, and Eli Lilly.

These setbacks have raised questions about whether the problem lies in the biology of tau itself or in which portions of the protein have been targeted to date.

According to researchers quoted in recent coverage of the Clinical Trials on Alzheimer’s Disease (CTAD) 2025 meeting, one view is that the lack of success may reflect differences in epitope selection. Some investigators argue that certain regions of the tau protein—particularly those associated with seeding and intercellular spread—may be more relevant to Alzheimer’s pathology than the epitopes chosen for earlier antibodies. This idea is driving the design of newer candidates now entering or progressing through early-stage trials.

At the same time, scientific leaders interviewed for the same reports noted a broader shift across the field. While amyloid and tau remain important research targets, a growing proportion of the Alzheimer’s pipeline now focuses on other biological pathways, including neuroinflammation, immune regulation, and vascular dysfunction. Companies pursuing these mechanisms include programs aimed at modulating regulatory T cells, reducing inflammatory signaling, or preventing vascular-associated inflammatory cascades. Several of these approaches are in phase I or phase II development.

Overall, experts described the environment at CTAD as one of cautious optimism. Despite recent disappointments in tau-directed programs, the expansion of therapeutic strategies and the diversity of mechanisms under investigation suggest that the next phase of Alzheimer’s drug development may extend well beyond traditional targets.

Click through the slides below for a quick overview of new AD targets and the new drug pipeline.

Background

McKenize H. Eisai Still Confident in Anti-Tau Asset as J&J Becomes Latest Victim in Spiraling Space. BioSpace. December 5, 2025. Accessed December 8, 2025. https://www.biospace.com/drug-development/eisai-still-confident-in-anti-tau-asset-as-j-j-becomes-latest-victim-in-spiraling-space