Biogen’s Aduhelm controversy as a case study for accelerated approval biomarkers in Alzheimer’s and related diseases

Alex Berg*, Ryan P. Mayers*, and Sarah Richards*

Edited by Sharon Jiang and Friederike M. C. Benning

Article | Aug. 29 2022

*Emails: alexberg@mit.edu, ryan.mayers@som.umaryland.edu, sarahevrichards@gmail.com

DOI: 10.38105/spr.y9p3sxuqg1

Highlights

The recent approval of Aduhelm, a medicine indicated for Alzheimer’s disease, sparked controversy in part due to reliance on biomarkers instead of primary data showing cognitive improvement

The use of biomarker surrogate endpoints enables medicines to make it from bench to bedside faster but reduces the certainty that these medicines show clinical efficacy

Future policy should build on the lessons from the Aduhelm approval, consider how biomarkers are chosen, and balance the risk of using biomarkers with their potential benefit to patients with neurodegenerative diseases

Article Summary

In June 2021, the United States Food and Drug Administration (FDA) approved Biogen’s Aducanumab (brand name Aduhelm) as the first purported therapy to directly impact Alzheimer’s disease (AD) progression. While such a therapy was a long-awaited goal in AD treatment, Aduhelm’s approval quickly became controversial due to the fact that its approval was based upon the drug’s ability to clear protein aggregates rather than any observed clinical outcomes for patients. These aggregates had been established as a surrogate endpoint, a probable marker of future clinical outcomes, but the decision to do so was controversial. Furthermore, now that Aduhelm has been approved, considerations about the precedent set by these surrogate endpoint choices now have ramifications for future AD drugs, drugs for other neurodegenerative diseases, and the FDA’s Accelerated Approval Program. In this review, we introduce the concept of biomarkers for surrogate versus clinical endpoints, explain why surrogate endpoints are necessary for many diseases like AD, why the endpoints selected for Aduhelm were controversial, and discuss how more appropriate biomarkers can be chosen for future AD and Accelerated Approval drugs.

Open Access

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Alex Berg

Computation and Cognition, Computer Science and Artificial Intelligence Lab of MIT, Cambridge, MA 02139, USA

Ryan P. Mayers

Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA

Sarah Richards

Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA

MIT Science Policy Review