Tsukamoto Katsura
Global Regulatory Science, Gifu Pharmaceutical University, Gifu, Japan.
Clin Ther. 2015 Aug;37(8):1652-60. doi: 10.1016/j.clinthera.2015.02.024. Epub 2015 Mar 21.
The incidence of Alzheimer's disease (AD) has been steadily increasing worldwide. AD is a serious disease that has both societal and economic impacts. The greatest risk factor for AD is aging. Thus, because of the rapidly aging population in Japan, the development of new, effective drugs for AD is urgently needed. The goal of the present article was to analyze the status, clarify the problems, and discuss the scientific and political challenges of disease-modifying drug development for AD.
Public data, official documents, literature, and news releases were surveyed and discussed.
Compared with diabetes mellitus drugs, there is a lack of quantitative surrogate end points among AD drugs. Much AD drug development has focused on amyloid-β and its associated pathways; however, these drugs have not shown efficacy in Phase III clinical trials. Thus, the US Food and Drug Administration has appealed for a new draft industrial guidance for the development of AD drugs, including those for early-stage AD. In Japan, the Minister of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency have also taken action, including the publication of potential new guidelines for clinical evaluation and development of new AD therapeutics, including drugs. Moreover, scientific initiatives to develop novel AD drugs are ongoing.
The development of quantitative surrogate end points remains necessary to improve the development of AD drugs. Therefore, collaboration among industry, government, and academia should be encouraged. Following the principles of regulatory science, strategies to develop drugs for illnesses with unmet needs can be framed by investigating the effects of past, current, and future AD drug development initiatives.
阿尔茨海默病（AD）在全球的发病率一直在稳步上升。AD是一种具有社会和经济影响的严重疾病。AD最大的风险因素是衰老。因此，由于日本人口老龄化迅速，迫切需要开发新的、有效的AD药物。本文的目的是分析现状、阐明问题，并探讨AD疾病修饰药物研发的科学和政治挑战。
对公共数据、官方文件、文献和新闻稿进行了调查和讨论。
与糖尿病药物相比，AD药物缺乏定量替代终点。许多AD药物研发都集中在淀粉样蛋白-β及其相关途径上；然而，这些药物在III期临床试验中并未显示出疗效。因此，美国食品药品监督管理局呼吁出台一份新的AD药物研发行业指南草案，包括针对早期AD的药物。在日本，厚生劳动省大臣和药品医疗器械局也已采取行动，包括发布新的AD治疗药物（包括药品）临床评估和研发的潜在指南。此外，开发新型AD药物的科学举措正在进行中。
开发定量替代终点对于改善AD药物的研发仍然很有必要。因此，应鼓励行业、政府和学术界之间的合作。遵循监管科学的原则，可以通过调查过去、当前和未来AD药物研发举措的影响，来制定针对未满足需求疾病的药物研发策略。
