非酒精性脂肪性肝炎创新药物非临床药效学研究的思考  

Consideration on pre-clinical pharamacodynamic evaluation of non-alcoholic steatohepatitis innovative drugs

作　　者：王士奇 宁娜 周宇 尹茂山 王寅 戎怿 周围 笪红远 王庆利 叶旋 WANG Shi-qi;NING Na;ZHOU Yu;YIN Mao-shan;WANG Yin;RONG Yi;ZHOU Wei;DA Hong-yuan;WANG Qing-li;YE Xuan(Center for Drug Evaluation,National Medical Products Administration,Bejing 100022,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国临床药理学杂志》2024年第22期3363-3368,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：有效性研究与评价是目前非酒精性脂肪性肝炎(NASH)药物研发中的关键问题。第1个NASH治疗药物Resmetirom基于病理学的替代终点获批上市,而多个NASH临床试验因未能达到肝组织学替代终点而中止。基于NASH的肝病理特征(气球样变性、小叶炎症、纤维化)设置非临床药效学评价指标,全面有效地开展非临床药效学评价是NASH适应证药物研发向前推进的重要保障。本文结合NASH治疗药物临床试验情况、NASH病理特点、疾病动物模型,探讨全面有效地开展NASH非临床药效学研究的必要性和可行性,以期为后续NASH药物研发的高质量发展提供帮助。Efficiency in pharmacodynamic study and evaluation is the critical issue in current drug research and development of non-alcoholic steatohepatitis(NASH).Resmetirom,the first marketed medicine for NASH,is approved by pathological surrogate endpoints,meanwhile several clinical trials suspended due to failure to achieve the liver histologic surrogateendpoints.Thewell-done non-clinical pharmacodynamic study basing on pathological features(ballooning degeneration,lobular inflammation,fibrosis)of NASH,is a great support to the whole research and development projects of new medicines for NASH.In this article,we discussed the necessity and feasibility of the NASH non-clinical pharmacodynamic study combining the clinical trials of NASH drug,the pathological features and the animal models of NASH,in order to facilitate the high-quality research and development of NASH drugs.

关 键 词：非酒精性脂肪性肝炎 非临床药效学研究 疾病动物模型 肝纤维化指标 

分 类 号：R97[医药卫生—药品]