Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019

Section:

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DOI: https://doi.org/10.1002/alz.12213
URL: https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.12213
ISSN: 1552-5279
page: 696-701
type: article-journal
issue: '4'
title: 'Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and
  ENGAGE trials as reported by Biogen, December 2019'
author:
  - given: David S.
    family: Knopman
  - given: David T.
    family: Jones
  - given: Michael D.
    family: Greicius
issued:
  - year: 2021
source: Wiley Online Library
volume: '17'
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.
language: en
title-short: Failure to demonstrate efficacy of aducanumab
container-title: Alzheimer’s & Dementia
---

is an academic article analyzing the results of recent clinical trials for the Alzheimer drug aducanumab (ADU).  It was published by Alzheimer’s & Dementia, the Journal of the Alzheimer's Association on November 1st, 2020. It was authored by David S. Knopman, David T. Jones, and Michael D. Greicius.  It argues that there is currently insufficient evidence in support of its use [@Ix4D05E7], and that a new phase III trial is required.

[In sum | In sum, the data from the EMERGE and ENGAGE trials, as presented by Biogen to date, do not support the conclusion that ADU has clinical benefits]. In sum, the data from the EMERGE and ENGAGE trials, as presented by Biogen to date, do not support the conclusion that ADU has clinical benefits. Further study is needed.

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