Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019
Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019
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DOI：
10.1002/alz.12213
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发表时间：
2020-11-01
影响因子：
14
通讯作者：
Greicius, Michael D.
中科院分区：
文献类型：
--
作者：
Knopman, David S.;Jones, David T.;Greicius, Michael D.
Aducanumab 最近进行了两项大型 III 期临床试验，但被赞助商百健 (Biogen) 提前终止。一项试验的结果呈阳性，而另一项试验则显示阿杜卡单抗没有任何益处。事后分析使申办者断言，有足够的疗效信号来证明新药应用作为治疗阿尔茨海默病的合理性。申办者声称，接受足够高剂量阿杜卡单抗的参与者子集在两项试验中都显示出益处。相比之下，我们在事后亚组中确定了与剂量效应无关的明显药物益处的替代解释。生物标志物数据与目标参与度一致，但没有证据表明生物标志物变化与认知益处相关。我们的分析支持使用高剂量阿杜卡单抗进行第三项 III 期试验。 Aducanumab 作为治疗阿尔茨海默病认知功能障碍的疗效无法通过具有不同结果的临床试验来证明。
Aducanumab recently underwent two large phase III clinical trials that were stopped prematurely by the sponsor Biogen. One trial was trending positive while the other showed no benefits from aducanumab. Post hoc analyses led the sponsor to assert that there was a sufficient efficacy signal to justify a new drug application as a treatment for Alzheimer's disease. The sponsor claimed that subsets of participants receiving sufficiently high doses of aducanumab demonstrated benefits in both trials. In contrast, we identified alternative accounts for the apparent drug benefits in post hoc subgroups that are unrelated to dose effects. Biomarker data were consistent with target engagement, but no evidence was presented to correlate biomarker changes to cognitive benefits. Our analysis supports the conduct of a third, phase III trial with high-dose aducanumab. Aducanumab's efficacy as a treatment for the cognitive dysfunction in Alzheimer's disease cannot be proven by clinical trials with divergent outcomes.