There is a long way to go in the research and development of innovative drugs in China. Why are these innovative drug companies becoming the model of new drug research and development in China?

Many years ago, the intuitive impression of China's pharmaceutical industry to the world was "cheap API supplier" and "low-end generic manufacturer" The so-called title of the world's largest producer and exporter of APIs is not a proud honor Wen Yang Chao has a long way to go in the research and development of innovative drugs in China, but he is also ready to be spared As the Wall Street Journal stated in China energies as powerhouse for biotech drugs, China is becoming the backbone of the development of international biotech drugs According to the data from the National Institutes of health, China has the second largest number of clinical trials in the world Photo source: national policy support and capital investment of the Wall Street Journal help innovative drug research and development During the 13th Five Year Plan period, the state strives to "change" in the implementation of major new drug projects, which can be seen in the special investment of new drugs According to Sang Guowei, academician of the Chinese Academy of engineering and President of the Chinese Pharmaceutical Association, China's total investment in new drug projects will reach 26 billion yuan by 2020 In recent years, the growth rate of China's pharmaceutical research and development has jumped to the first place in the world, and the innovation output and capacity have been improved rapidly A number of domestic pharmaceutical innovative R & D strength group enterprises are the best examples The strong R & D strength and unique business model of these enterprises truly explain the transformation from domestic new drug R & D enterprises to innovative ones, which is the general trend towards the world stage Unique business model, incubating innovative drugs made in China When approving new drugs to market in China, CFDA mainly considers the non inferiority of secondary end point and primary end point, and requires more for phase III clinical trials, including effectiveness and safety trials The approval rate of innovative tumor drugs developed by Chinese enterprises that have passed phase III clinical trials is very high Such as Chipscreen, Simcere and beta pharma In April this year, the new news came from xidaban, a microchip organism The clinical trial of breast cancer in Taiwan has successfully entered phase III As the first domestic anti-T-cell lymphoma new drug, cedarboxamine is a new molecular body with global patent protection independently developed by China's innovative drug R & D enterprise microchip biology, the first approved and listed subtype selective histone deacetylase oral inhibitor in the world, and also the first original new drug authorized by China and other developed countries such as the United States In December 2014, cidabamide, which has been developing for more than ten years, was approved by CFDA for listing, which is the first original new drug developed synchronously in the world in China Micro core biology chooses a strategic route originated from China's discovery and global synchronous development to carry out international research and development in the United States, Japan and Taiwan In 1999, Xiansheng Pharmaceutical Co., Ltd initiated the research and development of endu (recombinant human endostatin), successfully solved the problem of endu protein refolding, and began to prepare samples In 2000, it successfully entered various preclinical trials and clinical trials In 2004, the clinical studies were all completed, and in 2005, it obtained the CFDA new drug certificate In 2006, the recombinant human endostatin injection was approved by CFDA for marketing, and the trade name was endu This is not only the first anti-tumor molecular targeted drug approved for marketing in China, but also the first anti-cancer drug of endostatin in the world, which has obtained domestic and foreign patents 2017 is the 18th year since the project of "edu" was initiated in 1999 According to the US clinical trial database, more than 100 clinical studies have been registered by edu "Punabrin" is ready to launch as a technical team composed of excellent scientists from China and the United States, beyo ndspring NASDAQ: Bysi) has created a new business model for innovative pharmaceutical enterprises integrating resources from China and the United States and operating globally It makes full use of the advantages of China and the United States in new drug research and development, with high efficiency and low cost, and conducts global multi center phase III clinical trials at the fastest speed, so as to develop products with global commercial value As the first new drug R & D company established and operated by Chinese on the world stage for the global market, Wanchun pharmaceutical aims to submit class 1 new drug application to FDA and CFDA At present, the application for phase III clinical trial of panabrin has been approved by FDA and CFDA Among them, the listing of the drug in the Chinese market will be carried out according to the same route of approved tumor drugs such as xidaban, through the production of panabrin by Chinese contract manufacturers, to obtain the accelerated follow-up review and approval of national priority review drugs To explore the mechanism of drugs from the perspective of phenomena, solid basic research is needed Objectively speaking, behind the gratifying phenomenon that the output and capacity of pharmaceutical innovation in China have been rapidly improved, the overall contribution to global pharmaceutical innovation is still less than 5%, and there is still a gap with the international pharmaceutical giants In recent years, it is not difficult to find the target of class 1.1 new drugs that have been listed and declared in China It is basically the tracking innovation on the known target, which further reflects that the basic research and transformation research in China are relatively weak, and the real innovation ability is not strong In fact, 50% of new cancer drugs approved on the market are extracted and optimized from nature For the discovery of new compounds such as panabrin, Dr Huang Lan, founder of Wanchun pharmaceutical, believes that new drug research and development is actually a process of exploring the essence from the phenomenon, and exploring the mechanism of drugs is one of the thresholds for innovative drug research and development This is a long process full of unknown The most typical example is the Revlimid originally developed by celgene to treat multiple myeloma In 2015, the global sales reached 7 billion US dollars Behind the huge market potential, it took 50 years from the discovery of such compounds to the elaboration of the final mechanism As a class 1.1 new drug with global independent intellectual property rights, pranabline can alleviate neutropenia and play an effective role in "whitening" Since 2010, Wanchun began to study the mechanism of action of the most effective and safe compound found from nearly 300 derivatives The mechanism of punabrin was not known at first because it was extracted from marine organisms and optimized However, Wanchun medicine has mastered its unique immune mechanism in a relatively short period of time In addition to the team's own strong basic research strength, experts and professors from research institutions also add a lot of color to this This is also a very important point for the domestic pharmaceutical enterprises that are transforming to the research and development of innovative drugs to learn "If we know why this candidate drug is effective and explore its mechanism of action, then we can develop more indications and carry forward the role of this drug." ——Huang Lan for a potential candidate drug, how to design clinical and corresponding indications determines the first step of this drug towards the future market development Taking pranabulin as an example, through changing tumor microenvironment, including promoting the maturation of dendritic cells, activating T cells related to tumor antigens, inhibiting the aggregation of tubulin, swelling the endothelial cells of tumor blood vessels and starving the tumor by inhibiting tumor blood flow This is to explain the triple action mechanism of the phenomenon of "whitening up" of pranablin In this regard, Wanchun pharmaceutical takes the market position of "coordination in standard treatment" Three kinds of clinical trials are designed: one is to combine chemotherapy with chemotherapy, which is suitable for all neutropenia caused by chemotherapy At present, the clinical study of pranabulin in the treatment of chemotherapy-induced leukopenia is starting in phase II / III; the second is the combination of pranabulin and docetaxel in all indications (non-small cell lung cancer, gastric cancer, breast cancer, head and neck cancer, prostate cancer); The third is the combination of PD-1 / PD-L1 antibody in PD-1 indications (non-small cell lung cancer, melanoma, renal cancer) In general, neutropenia and non-small cell lung cancer are the two main indications for the application of pranabline These are two potential disease indications Because tumor chemotherapy often causes myeloid granulocyte inhibition, resulting in neutropenia It is understood that in 2016, the total market of chemotherapy-induced neutropenia was about $7.3 billion, and the revenue of neulasta, Amgen's new anti-tumor chemotherapy side effect drug, reached $4.6 billion, but it only achieved 20% of the chemotherapy market, which shows the potential of this market As the largest cancer species in the world, the scale of lung cancer patients shows the potential of the market There are about 1.8 million patients diagnosed with lung cancer every year in the world, 221200 in the United States and 700000 in China in 2015 87% of lung cancer patients were non-small cell lung cancer In 2020, the market size of lung cancer will reach US $28 billion Lung cancer market competition and innovation are the way out According to the report on Market Research and analysis of antitumor drugs issued by Southern Institute of pharmaceutical economics, from 2010 to 2015, the market capacity of small molecule targeted drugs used in lung cancer market in China was 1.167 billion yuan, 1.228 billion yuan, 1.513 billion yuan, 2.112 billion yuan, 2.797 billion yuan and 3.231 billion yuan, respectively At present, three kinds of small molecule targeted antitumor drugs are mainly used in the treatment of lung cancer in China In the face of the expanding market, many domestic pharmaceutical companies adopt the mode of research and development of these three types of generic drug market However, when many restrictions on the entry of unlisted new drugs into China are simplified, and foreign innovative drugs enter the Chinese market, the market pattern may change, and independent research and development of innovative drugs for lung cancer treatment is the way out Taking Eisen medicine as an example, as a domestic pharmaceutical enterprise with relative R & D strength, it has a deep layout of lung cancer drug R & D, and its third generation of EGFR lung cancer targeting inhibitor, ivetinib maleate, has global compound patents, and at the same time, it has launched clinical research in China and the United States Innovation in sales mode, not necessarily no profit in medical insurance As a leading enterprise in China's lung cancer market, Beida Pharmaceutical Co., Ltd has independently developed a small molecule targeted anti-cancer drug, exetinib, which has full independent intellectual property rights Since its listing in 2011, its sales volume has been very optimistic In 2012, its sales volume reached 307 million yuan, in 2013, 475 million yuan, in 2014, 703 million yuan, in 2015, 913 million yuan, and in 2016, its sales volume reached 1.035 billion yuan In 2017, ektini was included in the national health insurance There is no doubt that Beida pharmaceutical industry is successful in the way of commercialization in China, and it is a model for domestic innovative drug R & D enterprises to learn The sales mode of Wanchun pharmaceutical to panabrin in China will refer to Beida pharmaceutical In Dr Huang Lan's opinion, although entering the medical insurance means that the price will be cheaper, for the low-cost small molecule drugs, entering the domestic medical insurance means that the market share will be larger, but in terms of cost, only the transportation cost and the low production cost of small molecule drugs, so the profit space is still very optimistic Different from Beida pharmaceutical, Wanchun pharmaceutical will find some large international pharmaceutical companies to cooperate in the U.S market This is the commercialization mode of Wanchun pharmaceutical innovation, because in the United States, the value of NDA for new drug listing approval is the largest, entrusted medicine