FDA position statement "Early Alzheimer's disease: Developing drugs for treatment, Guidance for Industry"
FDA position statement "Early Alzheimer's disease: Developing drugs for treatment, Guidance for Industry"
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DOI：
10.1016/j.trci.2018.11.004
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Harrison, John E.
中科院分区：
文献类型：
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作者：
Sabbagh, Marwan N.;Hendrix, Suzanne;Harrison, John E.
尽管在临床试验中投入了数十亿美元来开发治疗阿尔茨海默病的新疗法，但在过去的15年里，还没有开发出一种获批的治疗方法。在此期间，开发和测试了新类别的药物，包括单克隆抗体、γ -分泌酶调节剂、γ -分泌酶抑制剂、BACE抑制剂、RAGE抑制剂、烟碱激动剂、5HT6拮抗剂等。所有这些临床试验项目的一个常量是使用ADAS-cog作为确定疗效的主要量表。需要考虑的问题是，究竟是药物的靶标作用，还是检验疗效的临床试验措施。FDA在2018年发布了一份新的立场声明，告知该领域证明有效性的可能考虑因素，以打开批准之路。在这里，我们提出并评论了多种替代ADAS治疗fda指定的3期和4期阿尔茨海默病的方法。这些新结果正在目前的临床试验中得到验证，并可作为未来疗效的衡量标准。
Despite billions of dollars invested in clinical trials to develop novel therapeutics for Alzheimer's disease, no approved treatments have been developed in the past 15 years. In that span, new classes of drugs have been developed and tested, including monoclonal antibodies, gamma -secretase modulators, gamma -secretase inhibitors, BACE inhibitors, RAGE inhibitors, nicotinic agonists, 5HT6 antagonists, and others. The one constant for all of these clinical trials programs is the use of the ADAS-cog as the primary scale to determine efficacy. The question that needs to be considered is whether it is the target engagement of the drug or the clinical trial measure testing the efficacy. The FDA put out a new position statement in 2018 informing the field on possible considerations for demonstrating efficacy to open the path for approval. Here, we propose and comment on a variety of approaches that are alternatives to the ADAS for FDA-specified stage 3 and 4 Alzheimer's disease. These novel outcomes are being validated in current clinical trials and could be used as efficacy measures moving forward.