Alzheimer's disease drug development pipeline: 2020
Alzheimer's disease drug development pipeline: 2020
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DOI：
10.1002/trc2.12050
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发表时间：
2020-01-01
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
简介：阿尔茨海默病（AD）是一种日益严重的公共卫生问题，影响着全球数百万患者，每年花费数十亿美元。我们回顾了治疗AD的药物和生物制剂的临床试验。我们使用常见阿尔茨海默氏症和相关痴呆症研究本体（CADRO）对治疗靶点和作用机制进行分类。我们回顾了我们过去5年的年度管道报告，以提供对AD临床试验和药物开发的纵向见解。方法：我们回顾ClinicalTrials.gov截至2020年2月27日的www.example.com，并确定了目前正在开发的用于治疗AD的药理学药物的所有试验，这些试验在这个广泛使用的美国食品和药物管理局注册表中有代表性。结果：有121种药物在临床试验中用于治疗AD。29种药物在36项3期试验中，65种药物在73项2期试验中，27种药物在27项1期试验中。试验中的12种药物针对认知增强，12种用于治疗神经精神和行为症状。有97种药物正在进行疾病缓解试验。与2019年的管道相比，针对淀粉样蛋白或tau蛋白以外途径的疾病修饰剂的数量有所增加。讨论：2020年的管道在临床试验和治疗靶点方面有所创新，为AD药物开发计划取得更大成功提供了希望。对过去5年临床试验的回顾表明，非淀粉样蛋白靶点逐渐受到重视，包括炎症、突触和神经元保护、血管因子、神经发生和表观遗传干预的候选治疗。正在筹备中的重新利用的代理人有了显著的增长。
Introduction: Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action. We review our annual pipeline reports for the past 5 years to provide longitudinal insight into clinical trials and drug development for AD.Methods: We reviewed ClinicalTrials.gov as of February 27, 2020, and identified all trials of pharmacologic agents currently being developed for treatment of AD as represented on this widely used U.S. Food and Drug Administration registry.Results: There are 121 agents in clinical trials for the treatment of AD. Twenty-nine agents are in 36 Phase 3 trials, 65 agents are in 73 Phase 2 trials, and 27 agents are in 27 Phase 1 trials. Twelve agents in trials target cognitive enhancement and 12 are intended to treat neuropsychiatric and behavioral symptoms. There are 97 agents in disease modification trials. Compared to the 2019 pipeline, there is an increase in the number of disease-modifying agents targeting pathways other than amyloid or tau.Discussion: The 2020 pipeline has innovations in clinical trials and treatment targets that provide hope for greater success in AD drug development programs. Review of clinical trials over the past 5 years show that there is progressive emphasis on non-amyloid targets, including candidate treatments for inflammation, synapse and neuronal protection, vascular factors, neurogenesis, and epigenetic interventions. There has been a marked growth in repurposed agents in the pipeline.