Division of Psychiatry, University College London, London, UK.
Nat Rev Neurol. 2021 Nov;17(11):715-722. doi: 10.1038/s41582-021-00557-x. Epub 2021 Sep 17.
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.
2021 年 6 月 7 日，基于对降低淀粉样蛋白水平可能带来临床获益的合理预期，美国食品药品监督管理局（FDA）加速批准 aducanumab 用于治疗阿尔茨海默病（AD）。这一决定使 aducanumab 成为 2003 年以来首个获批用于 AD 治疗的新药，也是首个获批用于改变 AD 病程的药物。许多人质疑在批准决定中是如何考虑科学证据、专家建议以及患者和家属的最佳利益的。在本文中，我们认为，在获得批准之前，FDA 和百健公司对临床试验数据的共同解读——高剂量 aducanumab 具有显著的临床效果——规避了传统的科学审查，这一解读得到了曾是百健公司主要资金接受方的患者代表团体的大力支持，这引发了人们对监管机构内部监管俘获风险的担忧，认为保障措施不足以减轻这种风险。在此，我们回顾了导致美国食品药品监督管理局在 2021 年 6 月 7 日做出这一决定的事件，并考虑是否可以从中吸取任何经验教训。
