[Skip to Navigation]
Sign In
Viewpoint
March 30, 2021

Evaluation of Aducanumab for Alzheimer Disease: Scientific Evidence and Regulatory Review Involving Efficacy, Safety, and Futility

Author Affiliations
  • 1Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 3Department of Biostatistics, University of Washington, Seattle
  • 4Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
JAMA. 2021;325(17):1717-1718. doi:10.1001/jama.2021.3854

On November 6, 2020, a US Food and Drug Administration (FDA) advisory committee reviewed issues related to the efficacy and safety of aducanumab, a human IgG1 anti-Aβ monoclonal antibody specific for β-amyloid oligomers and fibrils implicated in the pathogenesis of Alzheimer disease.1 Given the importance of drug innovation for this common and often devastating disease, the abandonment of prior monoclonal antibodies targeting β-amyloid, and the clinical, regulatory, and market effects that approval of aducanumab could have, there has been significant interest in the development and regulatory review of aducanumab.

Add or change institution
2 Comments for this article
EXPAND ALL
New Alzheimer treatment
Michael Plunkett, MD MBA | Practice
Well written. Shows FDA. Advisory committee “follows the science.”
CONFLICT OF INTEREST: None Reported
Comment on “Evaluation of Adacanumab for Alzheimer’s Diesase”
Todd Lorenz, M.D. | Stanford SPARK Program
While I agree with the authors' thesis that adacanumab is not ready for approval, there are two features of their rationale that deserve further scrutiny.

First, they quote a post-hoc hypothetical “p” value for evaluating the results of the positive high dose comparison of study 302 of “higher than 0.21”. Statistics should be used to calculate results specified in a study protocol. In the case of study 302, two analyses were prespecified of a high and a low dose. The former was positive and the latter failed to meet statistical significance. Hypothetical “P” values should
not be used as a substitute for clinical judgment. Perhaps someday statistics and artificial intelligence will supplant clinical judgment as the best arbiter of such decisions, but we aren’t there yet.

The second is calling into question the close collaboration of FDA and company officials during the clinical development program. These interactions are absolutely critical for industry to understand the FDA’s thinking, particularly when developing drugs for indications of high unmet need such as Alzheimer’s disease. Proscribing such interactions would put the patients who volunteer for such studies and the capital needed to perform them at unnecessary risk of failure. We should be able to count on the objectivity of our FDA colleagues regardless of these necessary interactions.
CONFLICT OF INTEREST: Consultant for CytoAgents, Inc. and Filtricine, Inc., two privately owned, very early clinical stage biopharmaceutical companies. Former consultant for Tolerion, Inc. and Shift Pharmaceuticals, also privately owned, early stage biopharmaceutical companies. I own stock in Johnson & Johnson for over 25 years.
READ MORE
×