Abstract
On 7 June 2021, aducanumab was granted accelerated approval for the treatment of Alzheimer disease (AD) by the FDA on the basis of amyloid-lowering effects considered reasonably likely to confer clinical benefit. This decision makes aducanumab the first new drug to be approved for the treatment of AD since 2003 and the first drug to ever be approved for modification of the course of AD. Many have questioned how scientific evidence, expert advice and the best interests of patients and families were considered in the approval decision. In this article, we argue that prior to approval, the FDA and Biogen’s shared interpretation of clinical trial data — that high-dose aducanumab was substantially clinically effective — avoided conventional scientific scrutiny, was prominently advanced by patient representative groups who had been major recipients of Biogen funds, and raised concerns that safeguards were insufficient to mitigate regulatory capture within the FDA. Here, we reflect on events leading to the FDA’s decision on 7 June 2021 and consider whether any lessons can be learned for the field.
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K.Y.L. researched data for the article, made a substantial contribution to discussion of content, wrote the article and reviewed and edited the manuscript before submission. R.H. researched data for the article, made a substantial contribution to discussion of content and reviewed and edited the manuscript before submission.
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Glossary
- Accelerated approval
-
An FDA-instituted programme to allow drugs that treat serious conditions and that fill an unmet medical need to receive earlier approval on the basis of a surrogate end point considered reasonably likely to predict a clinical benefit.
- Breakthrough therapy designation
-
A process designed to expedite the development and review of drugs intended to treat a serious condition when preliminary clinical evidence indicates that the drug might represent a substantial improvement over available therapies on a clinically significant end point or end points, which can be a surrogate end point considered reasonably likely to predict a clinical benefit.
- Type C meeting
-
A formal meeting between the FDA and sponsor concerning the development and review of a product that does not fall within the scope of a Type A meeting (a meeting necessary for an otherwise stalled product development programme to proceed or to address an important safety issue) or a Type B meeting (a milestone meeting, such as an end-of-phase I or II meeting).
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Liu, K.Y., Howard, R. Can we learn lessons from the FDA’s approval of aducanumab?. Nat Rev Neurol 17, 715–722 (2021). https://doi.org/10.1038/s41582-021-00557-x
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DOI: https://doi.org/10.1038/s41582-021-00557-x
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