Only me only can save Chinese new drugs

Source: tongshuyi / Huang Zhenhua 2015-11-02 after more than ten years of follow-up practice of new drugs, I have done more than ten me too and me worse, but painfully found that this is self deceptive, expensive and ineffective labor In ten to fifteen years, a new drug has been developed and reproduced From a commercial point of view, there is no possibility of success of this drug Although the new drug model is simple, but the cost of development is as expensive as it takes a lot of time I don't want to do that now, and I hope you don't ——Huang Zhenhua's new medicine is the most difficult job in the world There is no shortcut The R & D cost of a new drug is about 2.6 billion US dollars, and the discovery of new drugs is also a big challenge for large pharmaceutical companies, because the input is more and more, but the output is lower and lower For Chinese pharmaceutical enterprises, based on the unmet clinical needs, the only way is to return to the basic purpose of new drugs, find new drugs from the clinical, and create a real me only new drug The first-in-class model of conventional model has high requirements Most projects are based on the progress of basic science This model has strong competitiveness, but the enterprises with insufficient experience and strength are easy to be treated as me too The fundamental reason why big pharmaceutical companies rush to make the first new drugs is the Matthew effect caused by the top advantage of the first new drugs in the market Once a new drug becomes the first new drug, other new drugs of the target will be me too, and the competitive advantage of the first new drug will be naturally reflected The so-called first in class of domestic enterprises are mostly the targets that foreign companies have researched for many years but have not made drugs or the old "new" targets that have not been recognized in schools Especially in the field of tumor, the targets are changing with each passing day Many targets have not been eliminated by other new targets before the ready-made drugs can be made Moreover, as long as this target is promising, large pharmaceutical companies are very easy to anti super, and the DPP4 inhibitor Merck anti super Novartis is a good example This model is not suitable for Chinese companies In fact, there is no difference in the mode of fast tracking new drugs (me too, me better, best in class), but it is hard to find a living space in the crack of the first new drugs Almost all Chinese companies adopt this new drug model The timeliness of this model is very strong, and there is a certain opportunity for the fast tracking new drugs within three years of the initial new drug listing, but they are still facing the suppression of Matthew effect, the first innovative drug; the fast tracking new drugs listed five years after the initial new drug basically have no opportunity, and their sales have not reached the peak when they are terminated by the generic drugs of the initial new drugs Most of the new drugs of me too (better, worse) of Chinese companies are more than ten years behind the first innovative drug Moreover, if such a model has the opportunity, why don't foreign companies push their back-up projects into the market at the same time of their own initial drug development? (most of the back-up projects belong to me better for their initial new drugs) or develop multiple module new drugs with the same target at the same time? Many companies regard the advantages of preclinical and clinical data compared with the initial new drugs as a me better In fact, there are more and more cases of such me better being eliminated after being put on the market For example, Bi's DPP4 drug linagliptin Of course, if you really have the ability to see the loopholes of the first drugs, find the optimization, evaluation methods and clinical development methods to make up these loopholes, and dare to invest a lot of money to expand the clinical use of the target mechanism, then the best in class can undoubtedly be a very effective research and development strategy, such as Lipitor But from the perspective of R & D, it is more difficult to find a better follow-up drug than the first drug in clinical practice than most R & D enterprises can imagine If the initial drug has obvious defects, such as short half-life and too large dose, the original company will definitely have follow-up drugs to solve these problems, basically no one else In conclusion, the risk of rapid drug tracking model is greater than that of first in class The big pharmaceutical companies spent 56 billion projects on the new model If they didn't do it, I'll give you the idea The gambling component of this model is too big It doesn't mean it will not succeed But first, answer these questions from the perspective of business: Why do big foreign pharmaceutical companies give up developing a valuable project and send it to Chinese companies for development? Because they don't understand the data of their own projects, they leave the opportunity to Chinese companies Do these people have the opportunity to work in the pharmaceutical field in the future? The R & D and sales teams of most foreign pharmaceutical companies in China are very strong, and they also attach great importance to the Chinese market Even if they are only suitable for Chinese projects, should they give them to the teams in China to develop and sell? Why don't big pharmaceutical companies take over valuable projects of small foreign companies? Why do foreign pharmaceutical companies choose Chinese companies with no new drug experience, no complete development team, and no technical platform to support the later development? In addition, many people are doing 505 (b) (2) project, which is compared to "climbing on the shoulders of giants" 505 (b) (2) the declaration is for those drugs that have been put on the market and have lost the monopoly period of the market The products include new indications, new combinations of approved active ingredients, new preparations, dosage forms, specifications, changes in the route or scheme of administration, etc After the expiration of patent drugs, the market has been compressed by 10 times How big is the market surrounded by many generic drugs? The preparation technology of most patent drugs has met the clinical needs 505 (b) (2) how big is the remaining gap in the application? There is no production and sales platform for Chinese companies in the United States Where is the competitiveness of engaging in such new drugs? 505 (b) (2) What are the opportunities in meeting the unmet clinical needs? The me only mode is a special first in class, but it has different qualities Ordinary first in class is easy to be me too, but me only will not be me too Me only has chosen a non competitive field to meet the clinical unmet needs This model needs more project research work to determine its me only status Although it is difficult to project, the market risk in the later stage is very small because there is no competition There are several ways of me only: first, the structure-activity relationship of drugs is very strict, and there is no other branch For example, the lithium salt used for depression, the closest sodium salt to it, has no other therapeutic effect except for hypertension Clopidogrel and oxazolidinone are also of this kind; secondly, the optimization route is not widely known If you have an exclusive animal model to screen the active compounds, then competitors don't know how to continue to optimize your first drugs, such as dimethyl fumarate, pirfenidone, ketamine and many other drugs can be counted as this type; third, the mechanism is unknown Now the mainstream mode is target centered, but this mode has a big disadvantage that it is very easy to be tracked and surpassed by competitors Clozapine belongs to this category You only know that the drug works well but you don't know why Me only mode new drugs may be the only feasible opportunity for Chinese companies to occupy a place in the international competition for new drugs, because no matter the white cat or the black cat, it is valuable to solve problems, and it is the hard truth to find a safe and effective new drug to meet the unmet clinical needs First of all, choose the right research area to focus on It's not easy to choose a field that suits you, but at least avoid entering a field where you don't have an opportunity For example, diabetes, cardio cerebrovascular, tumor, CNS, etc are not the conventional development fields of Chinese companies Chinese companies in these fields, if they have a strong marketing network, can try the strategies of first imitation and destroying peripheral patents; for example, making big fish in a small pond to study new drugs suitable for Chinese clinical needs according to the differences in Chinese clinical needs; Orphan drugs are more and more becoming the trend of new drug concern, especially orphan drugs that seriously affect the quality of life, such as IPF, will receive more and more attention in the future Glybera, the first gene therapy drug, is also one of orphan drugs Second, the moat law of building a unique technology platform There are no ready-made opportunities for new drugs, which need in-depth exploration Only by forming a unique technology platform, can competitive new drugs be obtained The process of building the core technology platform is the process of strengthening the competition barrier, similar to the wider the moat, the stronger the competitiveness, and the more opportunities to form international new drugs, which is the core competitiveness of new drug companies Me too is a mature and simple technology If we just modify the existing structure by means of pharmaceutical chemistry and obtain a patent, the idea of becoming a new drug is too simple Such a new drug does not need any core competitiveness, and anyone can complete it Third, there are qualified new drug management leaders Many returnees have not experienced the whole process of new drug research and development and have no experience in decision-making The simplification of new drug project is a common phenomenon in China New drug is a kind of commercial science, which must produce commercial value, so the process of new drug is meaningful Therefore, the leaders of the new drug team must have sufficient experience in business competition, be familiar with all aspects of the operation in the process of new drug research and development, effectively integrate all kinds of new drug resources, only emphasize the team, do not pay attention to the fundamental issues of project approval, and no matter how strong the team is, it is also ineffective labor At the core of this is that the leaders of the new drug team have their own unique new drug concept to discover the opportunities for new drugs in the future Because there is no fixed model of new drugs to be copied, there is no ready-made path to follow how to obtain a new drug with huge market value and exclusive Without profound thoughts and original opinions, the more investment in me too new drug mode, the greater the waste The first law of three new drug laws: no new drug with the same mechanism can compete with generic drugs The second law: first in class and me too (better) drugs always win the competition The third law: the law of risk conservation of new drugs The law of competition for new drugs for 30 years: research and development of new drugs need to predict the competition for 30 years in advance The R & D process from project approval to listing is more than 30 years, and the remaining patent is less than 10 years The post competition effect, including the maturity of alternative products, also needs 10 years If we don't consider the competition in the next 30 years when setting up the project, the new drugs will become a burden for the enterprise in the next 10 years The ten-year golden period of new drugs on the market can not realize the value of new drugs, at the same time, it will miss the next opportunity.