When the US Food and Drug Administration used the accelerated approval process to authorize the use of the antiamyloid drug aducanumab to treat Alzheimer's disease (AD), many people hoped this signaled a new era of disease-modifying treatment. But 2 years later, aducanumab's failure to launch provides a cautionary tale about the complexities of dementia and the need for a thorough and transparent review of the role that regulatory agencies and various stakeholders play in approving AD drugs. We highlight the events leading to aducanumab's controversial approval and discuss some of the key lessons learned from the drug's failure to deliver the hoped-for benefits. These lessons include the inherent limitations of antiamyloid strategies for a complex disease in which amyloid is only one of several pathological processes, the need for clinical trials that better reflect the diversity of communities affected by AD, the potential pitfalls of futility analyses in clinical trials, the need for greater transparency and other modifications to the approval process, and the dementia field's unreadiness to move from the highly controlled environment of clinical trials to the widespread and chronic use of resource-intensive, disease-modifying drugs in real-world treatment scenarios. People with dementia desperately need effective therapies. We hope that the aducanumab story will inspire changes to the approval process—changes that restore public trust and improve future efforts to deliver disease-modifying therapies to the clinic.

中文翻译：

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从 Aducanumab 批准用于治疗阿尔茨海默氏病的经验教训

当美国食品和药物管理局通过加速审批程序授权使用抗淀粉样蛋白药物 aducanumab 治疗阿尔茨海默病 (AD) 时，许多人希望这标志着疾病缓解治疗的新时代的到来。但两年后，aducanumab 的上市失败给人们敲响了警钟：痴呆症的复杂性以及需要对监管机构和各利益相关者在批准 AD 药物中所扮演的角色进行彻底、透明的审查。我们重点介绍导致 aducanumab 获得争议性批准的事件，并讨论从该药物未能实现预期效果中吸取的一些重要教训。这些教训包括针对复杂疾病的抗淀粉样蛋白策略的固有局限性，其中淀粉样蛋白只是几种病理过程之一，需要更好地反映受 AD 影响的社区多样性的临床试验，临床试验中无效分析的潜在陷阱，需要提高审批流程的透明度和进行其他修改，以及痴呆症领域尚未准备好从高度受控的临床试验环境转向在现实世界的治疗场景中广泛和长期使用资源密集型、缓解疾病的药物。痴呆症患者迫切需要有效的治疗。我们希望阿杜卡单抗的故事能够激发审批流程的变革——这些变革能够恢复公众的信任并改善未来向临床提供疾病缓解疗法的努力。