@article{1fa22316a1a146e7b5e48e49df088402,
title = "Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019",
abstract = "Aducanumab recently underwent two large phase III clinical trials that were stopped prematurely by the sponsor Biogen. One trial was trending positive while the other showed no benefits from aducanumab. Post hoc analyses led the sponsor to assert that there was a sufficient efficacy signal to justify a new drug application as a treatment for Alzheimer's disease. The sponsor claimed that subsets of participants receiving sufficiently high doses of aducanumab demonstrated benefits in both trials. In contrast, we identified alternative accounts for the apparent drug benefits in post hoc subgroups that are unrelated to dose effects. Biomarker data were consistent with target engagement, but no evidence was presented to correlate biomarker changes to cognitive benefits. Our analysis supports the conduct of a third, phase III trial with high-dose aducanumab. Aducanumab's efficacy as a treatment for the cognitive dysfunction in Alzheimer's disease cannot be proven by clinical trials with divergent outcomes.",
author = "Knopman, {David S.} and Jones, {David T.} and Greicius, {Michael D.}",
note = "Funding Information: Dr. Greicius receives dividend payments as a shareholder of SBGneuro. He receives research support from the NIH. Dr. Jones receives research support from the Minnesota Partnership for Biotechnology and Medical Genomics, and Race Against Dementia and the NIH. Dr. Knopman served on a data safety monitoring board for the DIAN study. He serves on a data safety monitoring board for a tau therapeutic for Biogen, but receives no personal compensation. He is a site investigator in the Biogen aducanumab trials discussed here. He is an investigator in a clinical trials sponsored by Lilly Pharmaceuticals and the University of Southern California. He serves as a consultant for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences but receives no personal compensation. He receives research support from the NIH. He is a member of the U.S. Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee and was recused from the November 6, 2020 advisory committee meeting. His views do not reflect any position of the advisory committee and represent his views alone. Funding Information: Dr. Jones receives research support from the Minnesota Partnership for Biotechnology and Medical Genomics, and Race Against Dementia and the NIH. Publisher Copyright: {\textcopyright} 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association",
year = "2021",
month = apr,
doi = "10.1002/alz.12213",
language = "English (US)",
volume = "17",
pages = "696--701",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "4",
}