治疗阿尔茨海默病的新药Aducanumab

Aducanumab:A new drug for alzheimer’s disease

2021年6月美国食品药品监督管理局正式批准aducanumab用于治疗阿尔茨海默病,这是继2003年以来首个针对疾病潜在病理生理学的治疗药物。Aducanumab是由渤建生物技术公司研发的一种人单克隆抗体,可以选择性地结合β-淀粉样纤维和可溶性低聚物,抑制β-淀粉样斑块(Aβ)的聚集。渤建公司曾在2019年3月宣布该药的Ⅲ期临床试验失败并提前终止,但同年10月22日又意外地宣布该药物经过重新分析后,呈现出显著疗效,在多个试验组中,高剂量组(10 mg·kg^(-1))患者的大脑中Aβ斑块减少最显著,最常见的药物不良反应为淀粉样蛋白相关的影像异常,表现为水肿或含铁血黄素沉积。Aducanumab的突然上市引起了专家学者届的大量争议,主要集中在药物疗效和安全性方面。本文现从aducanumab的药理研究、临床研究、药代动力学、安全性和局限性等方面做一综述,以帮助临床全面了解该药物的研究现状和已有成果。

In July 2021, Food and Drug Administration officially approved aducanumab which is the first drug for the pathophysiology of the disease since 2003 to treat patients with Alzheimer’s disease( AD).Aducanumab is a human monoclonal antibody researched by Biogen,that selectively binds to amyloid beta( Aβ) fibrils and soluble oligomers,thus inhibits the aggregation of Aβ. In March 2019,Biogen announced the failure of aducanumab in phase Ⅲ trials and halted its development.However,on Oct 22,Biogen made an announcement that the trials showed exciting outcomes through reanalysis. Aβ reduced significantly in high-level groups( 10 mg·kg^(-1) in comparison with other groups and the main adverse events were amyloid related imaging abnormalities,including edema and hemosiderin deposition. The sudden launch of aducanumab induced a great deal of debates concentrating on its efficiency and safety in expert community. This paper provides a brief review of pharmacological research, clinical research, safety,limitations,etc. of aducanumab to help make sense of its current research status and results.