How can domestic innovative drugs start the golden decade?

In the end of October 2019, at the first global biomedical cutting-edge technology, policy and regulation conference held by tongshuyi, Dr Wang Yinxiang recalled to reporters the situation when he returned to China in 2003 to start his own business "At that time, the mainstream domestic pharmaceutical companies concentrated on generic drugs, and there were very few innovation attempts There was no venture capital fund specifically for innovative drugs, and most of the experiments needed cooperation with scientific research institutes, It's hard to find the right talent " Many people regard 2015 as a turning point for the development of domestic innovative drugs Since the "4 + 7" centralized procurement pilot at the end of 2018, new drug R & D seems to be an irreversible trend for the sustainable development of domestic pharmaceutical enterprises, with technology, capital and talents pouring in one after another In August 2019, as the first original research drug enterprise applying for the listing of science and technology innovation board, micro core biology officially landed in the public capital market; in November, Hengrui pharmaceutical released a notice that RMB 1.16 billion won two original research heavyweight new drugs in the clinical trial stage At least from the perspective of capital, the domestic new drug R & D industry is forming an innovation ecological chain similar to the mature markets in Europe and the United States However, is the innovation ecology of new drug research and development really formed in China? What other issues should be paid attention to in the rapid development of biomedicine in the next decade? After collecting opinions from industry personages, investment institutions and regulators, the reporter of arterial network found the following answers 1 There is a small gap between domestic and foreign drug development; 2 Industrial M & A has appeared, but its activity is low; 3 Clinical research is restricting the innovation process of original drugs; 4 Detour overtaking is a false proposition, and new drugs of me too will still be the mainstream trend in the future Junlian capital is an early institution engaged in innovative drug investment in China Hong Tan, managing director, observed that in the past 10 years, the mindset of investors and pharmaceutical companies has changed significantly From 2011 to 2014, almost no one will invest in new drug projects, but after 2015, there has been a roller coaster transformation New drug R & D enterprises with certain technical barriers are in hot demand, and the valuation has also risen After the "4 + 7" centralized purchase policy was settled, the traditional big pharmaceutical enterprises changed their mindset In the past, the strategy of making progress in the stability of generic pharmaceutical innovation rapidly turned to new drug research and development In fact, in recent two years, the regulatory side has also complied with the industrial changes and made many adjustments in line with international standards From the definition of innovative drugs to the priority of approval, they are trying to narrow the gap between domestic and foreign One manifestation of the narrowing gap is the increase in the number of patents Dr Wang Yinxiang pointed out that China's R & D level has entered the second echelon of the world in terms of the number of innovative drug patents However, it should also be noted that domestic pharmaceutical companies do not have global competitiveness in terms of sales channels At present, many domestic biotechnology enterprises are gradually narrowing the competition gap with multinational pharmaceutical enterprises in the downstream link of new drug research and development through the way of global multi center clinical trials According to incomplete statistics, more than ten original drug research projects are conducting multi center clinical trials in China, the United States, Australia and other parts of the world, and the time gap between the domestic and foreign new drug market has been shortened from the past decades to the fastest years in the near future However, sun Kuiyong, academician of the American Academy of engineering and chairman of force life science, mentioned the possible risks of accelerating new drug research and development The cycle of new drug research and development is very long, and new data will be available every moment Once the data is excessively compressed, various problems may occur To judge the R & D strength of a biotech enterprise, we need to see the backstage scientific ability through catching up, because drug R & D is to a large extent a test of the team's problem-solving ability At present, the small-scale biotechnology enterprises are the main force of domestic drug innovation In the competition with multinational pharmaceutical companies, biotechnology companies with significant technological advantages can show efficiency advantages in terms of centralized R & D investment and global clinical trials, and often achieve faster R & D and clinical trials progress on specific targets However, the weakness of biotechnology companies in global sales is also very obvious, which will undoubtedly restrict the long-term development of enterprises In the United States, large pharmaceutical companies and biotechnology companies integrate each other's advantages mainly through industrial mergers and acquisitions However, there are few mergers and acquisitions between Chinese enterprises, and the overall scale of industrial mergers and acquisitions is far behind the mature pharmaceutical market In Dr Wang Yinxiang's view, this is due to the fact that there are no large pharmaceutical enterprises with absolute strength in China The M & A of pharmaceutical industry involves billions of dollars, and the cash flow of large pharmaceutical enterprises will be under great pressure On the other hand, the R & D strategy of biotechnology enterprises is mainly to follow the innovation, the degree of product homogeneity is high, the global competitiveness is not strong, and it can not bring enough potential sales scale for the acquirer In the global new drug market, Chinese enterprises account for no more than 10% of the total, which has greatly hindered the industrial M & A At the same time, due to the relatively small number of high-quality targets and abundant capital pool, the valuation of biotechnology enterprises in the primary market is relatively high, which also limits the enthusiasm of large pharmaceutical enterprises for M & A to a certain extent However, industrial M & A is an indispensable part of the new drug innovation ecosystem On the one hand, new drug research and development is a process that needs to integrate resources at different stages to form a joint force On the other hand, according to statistics, there are more than 5000 pharmaceutical enterprises in China, and they maintain a high-speed growth Most of them have obtained at least one round of financing Considering that capital needs to exit channels, industrial merger and acquisition is also an important direction For a long time, as a large country of generic drugs, the demand of clinical trials in China has been restrained Then, after 2015, the consistency evaluation of generic drugs and the top-level design of encouraging new drug research and development will reflect the value of clinical trials, resulting in the dilemma of resource shortage He Ruyi, chief scientist of innovation medical health of SDIC, has many years of consulting experience in drug review institutions in China and the United States In his opinion, the current clinical trials in China are still in the initial stage, which is difficult to meet the needs of new drug research and development On the one hand, domestic researchers lack professional training in clinical trials, and there are few qualified clinical trial main researchers (PI), which has become a key link restricting the development level of domestic clinical trials In addition, there is a lack of supporting personnel in the clinical trial base, and many pharmaceutical companies are hard to find a truly competent clinical trial director The shortage of clinical trial talents is closely related to the limited number of clinical trial bases in China In the past, due to the consideration of the safety of clinical trials, the regulatory authorities were cautious about the audit of clinical trial bases, and the scope of opening up was very small According to the snowball statistics of the secondary market information disclosure website, before 2004, there were only 125 clinical institutions in China Since 2004, when the measures for accreditation of drug clinical trial institutions (for Trial Implementation) were issued, the number of clinical trial bases approved has increased significantly At present, there are about 600, but they are still far from meeting the needs of domestic new drug research and development and consistency evaluation In October 2017, the general office of the CPC Central Committee and the general office of the State Council issued the opinions on deepening the reform of the review and approval system and encouraging the innovation of pharmaceutical and medical devices, which clearly proposed that the qualification of clinical trial institutions should be subject to filing management After the institutions with clinical trial conditions register on the website designated by the food and drug administration, they can accept the entrustment of the applicant for registration of medical devices to carry out clinical trials Some analysts believe that the number of clinical trial bases is no longer the limiting step of innovative drugs and be tests, especially for generic drugs that recruit healthy people and only conduct bioequivalence test (be test), and the limit of clinical trial bases begins to be solved In addition, in the reform of drug review and approval system, it is emphasized to encourage international multi center phase II and phase III clinical trials to be conducted in China's trial base, hoping to promote the overall level of clinical trials in China by involving domestic clinical trial personnel in international clinical trials On the other hand, the industry standard of clinical trials in China has just been established In fact, clinical trials are not sophisticated and high-end trials, which can be completed by researchers with basic training However, the construction of rules and management system of clinical trials has just begun in China, and there are still many areas to be improved In July 2018, the State Drug Administration issued the announcement on adjusting the review and approval procedures of drug clinical trials (No 42 document), which not only meets the public demand for drug use and implements the responsibility of the applicant's R & D subject, but also embodies the policy guidance of encouraging innovation and accelerating the creation of new drugs, and makes clear provisions on how to improve the level of clinical trials in China At the scene of the Tonghua freehand brushwork conference, the topic of Chinese pharmaceutical enterprises overtaking in a curve was repeatedly mentioned The reporter of arterial network found the common point of view on this topic after questioning the industry personage, investors and regulatory experts respectively, that is, in the view of practitioners, it is a false proposition for Chinese pharmaceutical enterprises to overtake by turning in the next decade New drug research and development is a competition of comprehensive competitive strength, such as strength, speed, efficiency and so on It is impossible to surpass competitors with only one outstanding advantage More importantly, new drug research and development is a long-term accumulation process Many large pharmaceutical companies have established their own methodology through long-term exploration in the research and development of macromolecular and small molecule drugs Only by forming a unique methodology in practice can they win a place in the global market Hua Ye, founder / CEO of Yihui pharmaceutical, said that there is still fragmentation in the field of domestic innovative medicine, which needs to be integrated, passed on through his own experience and generations, and then ushered in a breakthrough Zhao Dayao, CEO of Youhe pharmaceutical, has worked in multinational pharmaceutical companies for many years and presided over the establishment of R & D centers in China by large foreign pharmaceutical companies He believes that in the next decade, domestic innovative drugs will occupy about 10% of the national pharmaceutical market, and me too innovative drugs will still be the mainstream "However, following innovation is not necessarily not encouraging If it can serve patients, it has great clinical value." Zhao Dayao pointed out Lu Xianping, chairman and general manager of micro core bio, who is the first to land in the public capital market, and Li Ning, executive director and general manager of Junshi bio, who is the first to promote the listing of domestic PD-1, have reached the same conclusion in judging the trend of me too innovative drugs Lu Xianping believes that in the next 10 years, the domestic pharmaceutical industry will present three characteristics: first, under the background of "4 + 7", local generic enterprises with excellent management capacity, production capacity, implementation capacity and coverage capacity will become important suppliers of generic drugs; second, in terms of innovative drugs, the largest majority of enterprises will continue to focus on me Too launched price competition, which partly met the clinical needs; third, some innovative enterprises joined the global competition through differentiated source innovation around the unsatisfied clinical needs Li Ning mentioned the importance of payment innovation in new drug research and development He pointed out that the domestic medical payment system is complex, and commercial insurance will make a major breakthrough in the next 10 years However, in the future, it is not impossible for domestic pharmaceutical companies to catch up with the United States in the level of research and development of first in class new drugs Among the 30 new drugs approved in the United States every year, 2-3 targets are covered From the perspective of new target discovery, the gap between domestic and foreign first in class is gradually narrowing In fact, new drug research and development needs to have self