简析仿创药向首创药的转轨

A concise analysis of switching generic drugs to first-in-class drugs

我国药物研究和制药工业的技术体系已经形成。以靶标为切入点的新药研制模式是以价值链的传递为特征,价值链的各个节点意味着价值增量,获得新药证书和生产批文是成功的重要标志,但更重要的是能够满足患者对无药可医或更加安全有效药物的需求。新(药物)分子实体(NME)可区分为首创性药物[即同类第一(FIC)]和仿创性的跟随性药物,前者包含靶标的发现和验证这一极其重要环节;后者具有跟随和模仿的性质,二者的技术含量有差别。我国研制仿创药物技术能力很强,迄今国产的NME大多数是仿创药,首创性药物极少。当前需要逐渐从仿创转轨到首创的道路。首创性药物的研制本质上是将生物学基础研究的成果经转化医学(价值链的传递)而获得成功。转化过程需要把握3个要素,即发病的分子机制、病患的宏观表象和微观特征、药物的作用机制。这3个要素相互关联,都是宏观表象和微观特征之间的转换与反馈,也是成功的保障。本文拟以成功的药物实例诠释这3个要素在新药创制中的作用。

The technology system of drug research and pharmaceutical industry has been built up in our country.The mode of target-based new drug creation is characterized by the transmission of value chain and each node of the chain means value increment of previous one.Although obtaining new drug certificate and production approval is an important sign of the success,more importantly,the patients’demand should be satisfied for incurable diseases or drugs that is more effective and safer.New molecular entities(NME)can be divided into pioneering drugs(FIC)and follow-up drugs(imitation).The former covers the extremely important link of target discovery and verification.The latter,however,features with imitation(me-too),and there are different technological contents between them.Our country possesses a strong technological ability to develop imitative drugs.Since the 21 st century,most of NME developed in China are me-too drugs,and few belong to FIC drugs.At present,it is necessary to gradually switch imitation to originality.In essence,the development of FIC drugs is the outcome of translational medicine starting from the basic biological research.The transformation process needs to grasp three elements:the molecular mechanism of disease,the macroscopic appearance and microscopic characteristics of disease,and the mechanism of drug action.These three elements are interrelated,which are the conversion and feedback between macro-appearance and micro-characteristics,and also the guarantee of success in R&D.This article tries to concisely explain the role of these three elements in the creation of FIC drugs with successful examples.