Professor of Psychiatry, Neurology, and Gerontology, Della Martin Chair of Psychiatry and Neuroscience Keck School of Medicine of USC Los Angeles, California
In this session we will provide an overview of clinical trials of anti-amyloid, monoclonal antibodies for Alzheimer’s disease and will discuss the biological rationale for their use, including their potential pathological targets. We will also describe the evolution of the phase 3 clinical trial designs for monoclonal antibodies that are used to demonstrate the required ‘substantial evidence for effectiveness’ needed for FDA marketing approval, including diagnostic eligibility criteria, sample sizes, treatment durations, clinical and neuropsychological outcomes, and the use of biomarkers for eligibility and as surrogate clinical outcomes. Additionally, we will review and analyze the two truncated and conflicting phase 3 aducanumab trials that formed the basis for FDA’s accelerated approval and will describe how this limited FDA approval necessarily led to CMS not covering aducanumab under Medicare.
Learning Objectives:
Discuss the rationale, study designs, and methods of preclinical and early-stage Alzheimer’s trials
List the basic outcomes and limitations of the phase 3 aducanumab trials
Describe the ethical considerations involved in the clinical use of aducanumab
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