Why can't China produce "blockbuster" drugs?

From the perspective of international market development, the "blockbuster" drug development model is gradually replaced by the precision medical model If domestic enterprises want to build a "heavy bomb", they need to solve not only the success of R & D listing, but also the improvement of global marketing ability The pharmaceutical industry often takes the "blockbuster" as a symbol of the successful development of a drug The annual sales volume of $1 billion has become a rigid standard for whether a drug has become a "blockbuster" If the annual sales volume exceeds $10 billion, the drug is often called "super blockbuster" But a decade ago, the threshold for a "blockbuster" was more than $500 million in annual sales In the last century, with the discovery and confirmation of one or more important targets, a batch of "heavy bomb" drugs will be born These drugs are milestone development and progress in the treatment of a disease Due to the in-depth study of medicine, new targets, new mechanisms are clarified, and finally a major breakthrough in drug discovery In addition to the epoch-making significance of the target on the market, the success of the "blockbuster" drug lies in its continuous follow-up research after the market Through the clinical comparative test, the development of new indications, the research of combination drugs, etc., it can consolidate its treatment status in the guidelines and further expand its market capacity From the perspective of indications, the drugs that can become "heavy bombs" in history are mainly international common diseases and frequently occurring diseases, with patent protection, wide adaptability, high efficacy, good drug safety and drug compliance, so as to occupy the mainstream disease status in the international mainstream countries It can be seen that the larger the population of potential patients corresponding to the disease, the greater the possibility of drugs becoming "heavy bombs" In terms of patent protection, all "blockbuster" drugs have applied for patents before they go on the market, and in order to extend the protection of intellectual property rights, enterprises will also apply for patents in line with policy incentives, such as technology, preparations, crystal forms, new children's indications, etc When the "blockbuster" drugs came into the market, there were several manufacturers with the same target drugs, just like the bidding manufacturers of hepatitis C therapy in recent health care negotiations At the initial stage of the new target drug market, most doctors and patients don't know about it, so it is necessary to develop a marketing strategy in line with doctors' cognition at that time to quickly open the market and promote doctors' prescription International pharmaceutical companies are also developing localized marketing strategies for different countries, cultivating local professional marketing teams and networks to ensure the market share of products in the world Luck is also a kind of "ability" to achieve "blockbuster" drugs For example, keytruda, a PD-1 drug (referred to as "K drug"), was not in clinical trials when MSD acquired Schering plough in 2009 After the merger and acquisition of MSD, the R & D asset was shelved Until the checkpoint inhibitor opdivo developed by BMS obtained promising R & D data, MSD was forced to reexamine K drug Opdivo is also BMS's unknown arrival at BMS when it acquired medarex BMS was more interested in yevoy, another tumor immunodrug, when the deal was launched In retrospect, the market size of CTLA-4 inhibitors is far smaller than that of PD-1 inhibitors After becoming a "blockbuster" drug, it can bring focus effect to the drug, the awareness rate of the drug will rise, and the brand awareness of the company will be greatly improved Blockbuster can generate sufficient and stable cash flow, and the performance will keep steady growth until the expiration of the patent period The secret of "blockbuster" maintaining high sales scale lies in its "patent protection", developing blockbuster drugs worth billions of dollars, and then fully defending the benefits of these drugs It can be seen from the expiration data of patent period that the number of special cases of "heavy bomb" drugs will gradually decline since 2022 Previous data reported that between 2013 and 2030, there were 1666 patents for compounds expired in the world Among them, 2014-2021 is the most concentrated year, with an average of more than 100 compound patents expiring every year Of the blockbuster drugs with annual sales of more than $1 billion, the core compound patents for eight drugs expired in 2015 and 2016 On the other hand, there are fewer and fewer products in the world whose sales match the "blockbuster" mark According to the forecast of corewellian, there are only 11 drugs capable of becoming "heavy bombs" in the next five years Among the 11 potential drugs, multinational pharmaceutical companies still account for 70% The decrease of "heavy bomb" drugs is due to the development of precision medicine The concept of precision medicine is aimed at the traditional integrated medical method The one-piece approach is that doctors will prescribe drugs to fight influenza as long as they are diagnosed with influenza A However, the causes of influenza A infection are various, and the absorption and metabolism of drugs in everyone's body are also different, which ultimately leads to different therapeutic effects in each patient Behind the precision medical treatment is the personalized drug demand Only a small number of patients need to develop new drugs, which is very different from the heavy bomb model As the patient stratification is becoming more and more accurate, the number of patients and the market for each approved drug are shrinking As the main treatment mode of rare diseases and anti-tumor, precision medicine, driven by precision medicine, first applies for listing through conditional listing license of rare diseases drugs, and then increases the indications through the real world Under the zigzag national salvation mode, rare diseases drugs become a new research and development hotspot Although a single rare disease drug is likely to fall short of the $1 billion threshold for blockbuster drugs, if a drug has multiple rare disease indications, it is likely to create new blockbuster sales In any case, the precision medical certificate promotes the change of the standard of "blockbuster" drugs: "the annual sales of blockbuster drugs is no longer the only standard to establish blockbuster identity Because the R & D and evaluation of drugs are becoming more and more efficient, less sales revenue can achieve the same return on investment as previously achieved blockbuster drugs " When the industry reviews the success of "blockbuster" drugs, there are often dramatic descriptions Such descriptions are like "gambling stone" success stories However, such a dramatic process often makes domestic pharmaceutical companies feel that they can succeed as long as they are lucky without professional judgment, and this model is worth imitating The imitated pharmaceutical companies always forget that the successful ones have more luck than their judgment, and the final success of the project is due to the experience of building "heavy bombs" accumulated by the enterprise itself People who have already succeeded are more likely to succeed again than those who have never succeeded for the first time At present, the local pharmaceutical enterprises are in the test of changing from imitated medicine to innovative medicine Many enterprises don't know what basic barriers they need to face for the first launch of new drugs These barriers can't be broken through by luck In 2018, the products with terminal sales of more than 6 billion yuan in China include budesonide, ambroxol, entecavir, piperacillin tazobactam, levofloxacin, cefuroxime, cefoperazone sulbactam, pantoprazole, omeprazole, acarbose, aspartic insulin, rabeprazole, sodium chloride, clopidogrel, low-molecular-weight heparin, oxiracetam, atorvastatin, and risu Valivastatin and amlodipine are equal At present, there is no new chemical drug independently developed in China Why doesn't China have a "blockbuster" drug? It is related to the fact that most Chinese pharmaceutical companies have not invested in the new drug field Without "4 + 7" volume procurement and "alliance expansion", Chinese pharmaceutical companies are more willing to invest in the field of generic drugs Even if the consistency evaluation is launched, the difficulty and risk of the whole project are relatively controllable for Chinese pharmaceutical companies to succeed in developing generic drugs and in the market However, if a new drug is made, the expensive project cost will lead to only two or three new drug products, and the same cost can cost 10 to 20 generic drug products Besides, it is easier to make generic drugs, with lower cost and higher approval rate Why challenge new drugs with higher difficulty, higher cost and higher risk? When the R & D willingness of enterprises is not high, the number of domestic enterprises that have new drugs on the market is not large, and the products with sales of more than 1 billion yuan are rare, and the new drugs that have been on the market are basically me too drugs The competition between these drugs and imported pharmaceutical enterprises in the domestic market is often more win than lose The reduction of profits of generic drugs forces Chinese pharmaceutical companies to invest resources in new drugs instead of generic drugs, which has a great relationship with domestic policy orientation In recent years, China has ushered in the best new drug R & D policy era in history with its favorable policies on new drug R & D, including accelerating the review and approval, dynamic adjustment of medical insurance, improvement of intellectual property system, and financial support from local governments at all levels In fact, when approving a drug, the drug regulatory department does not care whether it can become a heavy bomb after being put on the market, only whether it is safe and effective enough Health care payers also don't care whether a new drug can become a blockbuster, only whether it is better than the existing treatment, and whether it meets the reimbursement standard For enterprises, if they can get to the requirements of the regulatory authorities, they can really help a drug to be put on the market more quickly The investment pressure of a new drug project is mainly in the later stage of clinical trials Because there is no final layout of planning and compliance for clinical trials, individual domestic enterprises can't judge whether the clinical quality of their new drug products really conforms to the domestic listing standards, let alone what kind of clinical research should be launched by the enterprises after the listing before the products can be put into the market Provide clinical evidence during competition.