争议中的阿尔茨海默病药物Aducanumab

Controversy surrounding aducanumab for Alzheimer’s disease

Aducanumab是一个选择性识别β-淀粉样蛋白(Ab)聚集体的治疗性人源单克隆抗体。渤健先前的1期临床试验显示aducanumab减少脑内的Ab沉积并且延缓病人认知下降,这促使该公司在早期阿尔茨海默病患者中展开两项采用完全相同设计的3期临床研究EMERGE和ENGAGE。在2019年3月的无效分析显示试验失败以后,包括了额外三个月数据的进一步分析显示aducanumab似乎在EMERGE中达到了首要和次要临床终点,但在ENGAGE中无效。然而,对ENGAGE这个较EMERGE早开始一个月的临床研究的亚组分析显示该药有存在疗效的趋势。渤健认为新的分析因为考虑了临床方案修订的影响因而更加合理,并且计划于2020年初提交新药上市申请。这个急剧的反转引发了关于其采集的临床试验数据和所采用的分析方法的广泛热议。尽管2020年美国食品药品监督管理局(Food and Drug Administration, FDA)能否批准该药存在不确定性,当前的数据给饱受质疑的淀粉样蛋白假说提供了支持,更重要的是让数千万阿尔茨海默病患者看到了一些希望。

Aducanumab is a human-derived therapeutic monoclonal antibody selectively targeting aggregated β-amyloid(Aβ).Previous Phase l clinical trial by Biogen showed that aducanumab reduced Aβ deposition in the brain as well as slowed cognitive decline.This prompted two identically-designed Phase 3 clinical studies,EMERGE and ENGAGE,in early Alzheimer’s disease(AD)patients.After failing a futility analysis in March 2019,further analysis including three more months of data showed that aducanumab appears to have met its primary and secondary endpoints in EMERGE but not ENGAGE.However,a subgroup analysis of ENGAGE,which started a month earlier than EMERGE,revealed a trend towards efficacy.Biogen believes the re-analysis is valid because it took into account the effect of protocol amendments and plans to file new drug application in early 2020.Such a sharp turnaround incited a huge debate on the scientific rigor of the data collected and the analysis adopted by Biogen.Even though it is uncertain whether FDA will approve aducanumab in 2020,the data associated with it provides support to the increasingly-questioned amyloid hypothesis and even more importantly,some hope for the millions of AD patients.