Alzheimer's disease drug development pipeline: 2019
Alzheimer's disease drug development pipeline: 2019
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DOI：
10.1016/j.trci.2019.05.008
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Zhong, Kate
中科院分区：
文献类型：
--
作者：
Cummings, Jeffrey;Lee, Garam;Zhong, Kate
阿尔茨海默病（Alzheimer's disease，AD）的治疗方法很少，而且AD药物开发的失败率很高。AD药物开发管道的研究可以提供深入了解药物开发的演变，以及如何最好地优化开发practices.MethodsWe审查和确定所有药理学AD试验的所有代理目前正在开发的治疗AD。ResultsThere是132代理在临床试验中治疗AD。28种药物在42项3期试验中; 74种药物在83项2期试验中; 30种药物在31项1期试验中。与2018年管道相比，各阶段代理商数量均有所增加。试验中的19种药物针对认知增强，14种用于治疗神经精神和行为症状。有96种药物在疾病修饰试验中，其中38种（40%）将淀粉样蛋白作为主要靶点或作为几种效应之一。18种抗淀粉样蛋白药物是小分子药物，20种是单克隆抗体或生物疗法。7种小分子和10种生物制剂将tau作为主要或组合靶点（18%）。淀粉样蛋白是3期和2期疾病改良试验中最常见的特异性靶标。新的生物标志物（例如，神经丝光），新的结果（例如，AD综合评分[ADCOMS]）、早期人群入组和创新试验设计（例如，贝叶斯自适应设计）是最近的临床试验中的新功能。DiscussionDrug开发继续稳健的各个阶段，尽管在最近的过去几个程序的挫折。持续未满足的需求需要致力于增长和加速管道。
IntroductionAlzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices.MethodsWe reviewed and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD.ResultsThere are 132 agents in clinical trials for the treatment of AD. Twenty-eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase 1 trials. There is an increase in the number of agents in each phase compared with that in the 2018 pipeline. Nineteen agents in trials target cognitive enhancement, and 14 are intended to treat neuropsychiatric and behavioral symptoms. There are 96 agents in disease modification trials; of these, 38 (40%) have amyloid as the primary target or as one of several effects. Eighteen of the antiamyloid agents are small molecules, and 20 are monoclonal antibodies or biological therapies. Seven small molecules and ten biologics have tau as a primary or combination target (18%). Amyloid is the most common specific target in phase 3 and phase 2 disease modification trials. Novel biomarkers (e.g., neurofilament light), new outcomes (e.g., AD Composite Score [ADCOMS]), enrollment of earlier populations, and innovative trial designs (e.g., Bayesian adaptive designs) are new features in recent clinical trials.DiscussionDrug development continues robustly at all phases despite setbacks in several programs in the recent past. Continuing unmet needs require a commitment to growing and accelerating the pipeline.