生物标志物在阿尔茨海默病药物研发中的作用。
The Role of Biomarkers in Alzheimer's Disease Drug Development.
机构信息
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
出版信息
Adv Exp Med Biol. 2019;1118:29-61. doi: 10.1007/978-3-030-05542-4_2.
Abstract
Biomarkers have a key role in Alzheimer's disease (AD) drug development. Biomarkers can assist in diagnosis, demonstrate target engagement, support disease modification, and monitor for safety. The amyloid (A), tau (T), neurodegeneration (N) Research Framework emphasizes brain imaging and CSF measures relevant to disease diagnosis and staging and can be applied to drug development and clinical trials. Demonstration of target engagement in Phase 2 is critical before advancing a treatment candidate to Phase 3. Trials with biomarker outcomes are shorter and smaller than those required to show clinical benefit and are important to understanding the biological impact of an agent and inform go/no-go decisions. Companion diagnostics are required for safe and effective use of treatments and may emerge in AD drug development programs. Complementary biomarkers inform the use of therapies but are not mandatory for use. Biomarkers promise to de-risk AD drug development, attract sponsors to AD research, and accelerate getting new drugs to those with or at risk for AD.
摘要
生物标志物在阿尔茨海默病（AD）药物开发中具有关键作用。生物标志物可辅助诊断、显示靶点结合情况、支持疾病修饰，并监测安全性。淀粉样蛋白（A）、tau（T）、神经退行性变（N）研究框架强调了与疾病诊断和分期相关的脑成像和 CSF 测量，可应用于药物开发和临床试验。在将候选治疗药物推进至第 3 阶段之前，在第 2 阶段证明靶点结合情况至关重要。具有生物标志物结果的试验比显示临床获益所需的试验更短、更小，对于了解药物的生物学影响以及告知去留决策非常重要。治疗的安全和有效使用需要伴随诊断，这可能会出现在 AD 药物开发计划中。补充生物标志物可告知治疗的使用，但并非使用的强制性要求。生物标志物有望降低 AD 药物开发的风险，吸引赞助商开展 AD 研究，并加速将新药提供给 AD 患者或有患病风险的患者。
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