非酒精性脂肪性肝炎新药研发的回顾与思考  

Review and Reflection on the Development of New Drugs for Non-Alcoholic Steatohepatitis

作　　者：尹茂山 王寅 李峥 王士奇 尹华静 笪红远[1] 叶旋 YIN Mao-shan;WANG Yin;LI Zheng;WANG Shi-qi;YIN Hua-jing;DA Hong-yuan;YE Xuan(Centre for Drug Evaluation,National Medical Products Administration)

机构地区：[1]国家药品监督管理局药品审评中心

出　　处：《中国食品药品监管》2024年第7期26-35,共10页China Food & Drug Administration Magazine

摘　　要：非酒精性脂肪性肝病(NAFLD)已成为我国第一大慢性肝病。在NAFLD的各种表型中,非酒精性脂肪性肝炎(NASH)极有可能发展为包括肝硬化、肝癌在内的终末期肝病,导致由肝脏坏死引起的死亡率增加,这也是欧美等发达国家和地区采用肝移植术进行治疗的主要原因。目前NASH的治疗仍处在联合用药治疗的阶段,尚存在严重未满足的临床需求,除美国批准新药Resmetirom外,国内外再无其他NASH新药上市。NASH新药的成药性及其评价标准始终是最受关注的内容。本文通过分析NASH新药研发状况,反映出非临床药效学研究的支持性不足以及临床研究达不到终点评价指标对新药成药性的影响,也提示着非临床药效学研究结果是否支持用于NASH临床试验、临床试验研究能否达到评价终点是促进NASH新药开发进程的关键节点。Non-alcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease in China.Among the various phenotypes of NAFLD,non-alcoholic steatohepatitis(NASH)is highly likely to develop into end-stage liver diseases,including cirrhosis and liver cancer,leading to increased mortality.This is also the main cause of liver transplantation in developed countries or region in Europe and America.At present,the treatment of NASH remains in the form of combination therapy,and there are serious unmet clinical needs for targeted new drugs.Apart from the approval of the new drug Resmetirom in the United States,no other NASH new drugs are on the market domestically or internationally.The medicinal properties and evaluation criteria of NASH new drugs have always been of significant concern.The lack of support for nonclinical pharmacodynamics research and the impact of clinical trials not meeting endpoint evaluation indicators on the druggability of new drugs are reflected in the development status of NASH new drugs.This also suggests that whether non clinical pharmacodynamics research results support the use of NASH clinical trials and whether clinical trials can achieve evaluation endpoints are key factors in promoting the development process of NASH new drugs.

关 键 词：非酒精性脂肪性肝病 非酒精性脂肪性肝炎 有效性 成药性 回顾与思考 

分 类 号：R975[医药卫生—药品]