Affiliations: [a] Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA
| [b] Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| [c] Research & Development, Chiesi Farmaceutici, Parma, Italy
| [d] Section of Biophysical and Biomedicinal Chemistry, Technical University of Denmark, Kongens Lyngby, Denmark
| [e] Science Norms Democracy, UMR 8011 Sorbonne University, Paris, France
| [f] Bioethics Program, FLACSO Argentina, Buenos Aires, Argentina
Correspondence:
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Correspondence to: Dr. Timothy Daly, Bioethics Program, FLACSO Argentina, Tucumán 1966, C1050 AAN,
Buenos Aires, Argentina. E-mail: tdaly@flacso.org.ar.
Abstract: Three recent anti-amyloid-β antibody trials for Alzheimer’s disease reported similar effect sizes, used non-reactive saline as placebo, and showed large numbers of adverse events including imaging anomalies (ARIA) that correlate with cognitive changes. Conversely, all previous antibody trials were less reactive and pronounced ineffective. We argue that these observations point to unblinding bias, inflating apparent efficacy and thus altering the risk-benefit balance. Further, we highlight data demonstrating that beyond reducing amyloid, monoclonal antibodies increase monomeric amyloid-β42 in cerebrospinal fluid, which may explain potential benefits. We should recalibrate the efficacy of these antibodies and devote more resources into strategies beyond removing amyloid.
