肾脏疾病药物创新研发进展及思考

Research and Development on the New Drugs of Kidney Disease and Considerations

目的 探讨肾脏疾病药物创新研发特点、进展及关键技术考虑。方法 调研国内外药品监管机构监管进展及相关文献,梳理近10年国内外肾脏疾病药物上市及在研药物情况,分析研发特点及关键技术难点,并提出建议。结果与结论 2013年至今,中国及欧美批准肾脏疾病新药10个,近5年该领域新药临床试验申报量持续增长,尤以慢性肾脏病(chronic kidney disease,CKD)、免疫球蛋白A(IgA)肾病适应证申报居多。为更好地促进该领域药物创新研发,需关注以下方面:(1)进一步加强疾病发病机制等基础研究工作,助力筛选并开发新机制、新靶点,具有特异性治疗作用的新药,以期有效延缓乃至逆转疾病进展;(2)建议以患者需求为出发点,开发科学合理的临床结局评估工具,更好地评价患者获益;(3)肾脏疾病病因复杂,可考虑结合疾病流行病学及自然病史特征、药物特点及研究目的,选择具有代表性的患者人群;(4)肾脏疾病早期控制至关重要,但该病进展缓慢,临床终点的考察往往需要长达几年或更长的研发周期和较大的样本量,因此,探索、开发并验证替代指标具有较大的临床意义,但需审慎选择,必要时与监管机构沟通;(5)充分的安全性研究是获益-风险综合权衡的重要支持。

OBJECTIVE To discuss the characteristics of research and development on the new drugs of renal disease and technical considerations envolved.METHODS By investigating the advance of the regulatory agencies home and abroad and the related literature,the nephrotic drugs of the last decade in the market and in research were summerized domestically and overseas,the characteristics of research and key technical points were analyzed and relevant suggestions were put forward.RESULTS and CONCLUSIONS Ten new drugs have been approved by China,European Union and United States since 2013.The applications of the new drugs on this field has continued to increase in the recent 5 years,mainly on the chronic kidney disease and IgA nephropathy.To better promote the drug innovation development in this field,the following aspects should be paid attention to:The first is to further strengthen the basic scientific research about the pathogenesis of diseases,and screen the potential new drugs with new target and mechanism,so that make it possible to delay and even reverse the progression of the disease.The second is to better evaluate the patients beneifts by developing scientific and rational clinical outcome assessment tools with the basis of the patients′ needs.The third is to choose the representative population by the combination of epidemiology,natural history,the feature of drugs and the aim of clinical trials since the pathology of renal diseases is complicated.The fourth,early management of renal disease is crucial.So it′s of great significance to explore,develop and validate the surrogate endpoints since the disease progresses slowly and the investigation often requires both long study cycle of several years or even longer and a larger sample size.The surrogate indicators should be selected prudently.The sponsors are suggested to communicate with the regulatory agency when necessary.The fifth,a sufficent safety study can be very supportive to the general evaluation of benefit-risk balance.