At present, "China" has become one of the "hot words" in the global scientific and technological circles: top international academic journals produce special features for Chinese research; The World Intellectual Property Organization praises China\'s patent "blowout"; "New Four Great Inventions" in overseas "circle of fans" countless... China\'s innovation has become a new driving force for feeding global medicine, and its world significance has become more prominent. In particular, the opinions issued by the two offices on deepening the reform of the drug approval system and encouraging drug innovation and device innovation have sounded the horn of China\'s pharmaceutical innovation, and we have ushered in the golden age of pharmaceutical innovation.
On the morning of November 9, at the 29th National Pharmaceutical Economic Information Conference, a brainstorming session on the ecological change and trend research of pharmaceutical innovation was refreshing the cognition of more than 1,000 medical professionals on the future of the industry. Dr. Tao Jianhong, deputy director of CFDA Southern Institute of Pharmaceutical Economics and editor-in-chief of Pharmaceutical Economic News, in the theme report of "Global Pharmaceutical Innovation Characteristics and Chinese Trend Research and judgment", proposed for the first time the research and judgment of China\'s pharmaceutical innovation into the golden age, and let us jointly open the door of a new era with her, and explore the blueprint of future pharmaceutical innovation.
First, ten features of global pharmaceutical innovation ecology
In Tao Jianhong\'s view, the social environment and industrial foundation supporting the leap in China\'s pharmaceutical innovation have been perfected. On the one hand, China\'s medical and health services have made great progress. The proportion of total health expenditure to GDP has increased to more than 6%, the per capita health expenditure has tripled, the medical insurance coverage rate has exceeded 98%, and a consensus on clinical value-oriented research and development has been formed. On the other hand, in the five years since the 18th National Congress, the scale of China\'s pharmaceutical industry has continued to expand, and the proportion of total output value of the pharmaceutical industry in GDP has also increased from 3.2% to 4.3%. The top 100 pharmaceutical companies not only pursue scale expansion, but also pay more attention to innovation investment, especially the emergence of some entrepreneurial research and development enterprises, which has become the vitality gene of current industrial innovation.
1. The global pharmaceutical market is growing faster, with emerging markets leading the new growth
It is expected that from 2017 to 2022, the world prescription drug market will be driven by another round of new drug listing tide, maintaining an average annual growth of 6.5%, and the total scale will exceed one trillion US dollars by 2022.
In the past 10 years, the global pharmaceutical companies\' research and development costs have increased by more than 80%, while the number of new products launched has decreased by 43%. According to the report "How to Make Profits in the Pharmaceutical Industry" released by the world\'s top strategic consulting company Roland Berger Management Consulting, 75% of the surveyed companies said that they are experiencing a strategic crisis. The focus will be on high-growth emerging markets. The growth of the global pharmaceutical economy has shifted from developed countries to emerging market countries.
2. Domestic and foreign drug approval speed up, Chinese enterprises quickly follow up FDA new drug approvals
As of October 30, 2017, the FDA has approved a total of 35 new drugs, of which 4 have been declared in the domestic CDE. Since 2016, the number of new drug registration applications in China has accounted for 55% of the total drug registration applications. The backlog of drug registration applications has been basically eliminated, and the number of drug registration applications awaiting review has dropped from 21,668 in August 2015 to 3,000 in August 2017. Applications for clinical trials of antibiotics and vaccines and applications for registration of traditional Chinese medicine have been reviewed according to time limits.
3. International multi-center clinical acceleration, China ushered in the second wave of imported drugs
Under the new system, the domestic listing registration of imported new drugs has been adjusted, from the original three reports of three batches to two reports of two batches, and the review and approval of imported new drugs has been accelerated, with a total of 22 approved in 2016 and 51 approved from January to October 2017. As of August 14, 2017, 144 import acceptance numbers were included in the priority review. Imported hepatitis C new drugs concentrated landing in China, up to now, BMS, Johnson & Johnson, Gilead, AbbVie oral hepatitis C new drugs have been listed in the domestic market, the United States hepatitis C market experienced a rapid outbreak and rapid contraction, price competition is becoming increasingly fierce, to the domestic generic enterprises will also bring some pressure.
4. China joined ICH to open a new global R&D pattern, and pharmaceutical giants continued to increase R&D investment
In June 2017, CFDA became a full member of ICH, and through the synchronization of standards and guidelines, China\'s drug evaluation and approval standards will be more and more close to developed countries. The data show that in 2017, the geographical distribution of pharmaceutical R&D companies moved east as a whole: the number of new drug R&D companies in China increased from 4% (2016) to 5% (2017), and China has become the largest country for new drug research and development in Asia.
Pharmaceutical giant pharmaceutical companies continue to increase research and development investment, the total sales revenue of the top 20 in 2017 accounted for 41.7% of the world drug market, and the average research and development intensity of the top 20 enterprises in 2017 was 19.6%
5. The "buying doctrine" of new drugs is back in vogue, and large-scale mergers and acquisitions expand the R&D pipeline
Due to the high investment and high risk of research and development, the "buying doctrine" of new drugs has attracted more attention in recent years. Among them, large foreign-funded enterprises are more broad-minded in this measure. For example, Roche drove the company\'s development through mergers and acquisitions, and the proportion of pharmaceutical sales acquired increased from 77% of total sales in 2014 to 84% in 2017. BMS is the fastest growing company through outsourcing potential, with 61% of sales expected to come from acquired pharmaceuticals in 2020. Tao Jianhong suggested that mergers and acquisitions are generally used when enterprises want to enter new fields, which contribute greatly to the short-term revenue increase of enterprises, and can also share the risk of relying too much on the main research and development direction. However, if an enterprise wants to build a lasting business, it is also necessary to invest in research and development in its main business. Roche can have such a stable performance for a long time, and its continuous investment in the field of oncology drugs for many years can not be separated, only in 2016, five anti-tumor new drugs were approved by the FDA.
6. Foreign companies adjust the traditional early research and development model and inject new vitality into cooperation with innovative small pharmaceutical companies
In recent years, foreign pharmaceutical companies have closed or sold their research and development centers in China increasingly frequently. The main reason is that the research and development efficiency of large pharmaceutical companies is not high, and the traditional research and development model has begun to change, and instead cooperate with early research and development of small enterprises with higher research and development efficiency. In China, the cooperation between innovative pharmaceutical companies and foreign pharmaceutical companies is also gradually increasing, from 2000 to 2016, the average annual growth rate of Chinese pharmaceutical companies\' foreign transaction cooperation is 19%.
7.MAH connects start-ups with the pharmaceutical industry, and the global demand for pharmaceutical outsourcing rises
At present, the world\'s top 10 major pharmaceutical companies are basically external purchases of innovative early projects and later development. In China, the top 50 pharmaceutical companies have also set foot in the field of innovative drugs. At this stage, the Marketing Authorization system (MAH) implemented in China promotes collaborative innovation between start-ups and pharmaceutical companies. The domestic CMO/CDMO market has grown from $1.8 billion in 2011 to $5 billion this year, with a compound growth rate of 18.6%. It is expected that by 2020, the domestic market will reach 8.5 billion US dollars, accounting for about 9.7% of the global market.
8, the generic drug industry price pressure increased, "breakthrough" generic drugs to accelerate the listing process
Generic drugs will continue to face price pressure, in Teva\'s case, its shares fell 24% in August 2017, its core product multiple sclerosis drug Glatir faces a patent challenge, which is likely to result in the loss of exclusive product status, and Teva is also facing strong competition from rival Tecfidera. The Trump administration has repeatedly attacked drug prices for being too high, and the FDA has begun to greatly accelerate generic drug approvals, prioritizing applications for more than 100 breakthrough generic drugs, a move that has increased competition in the market while also lowering drug prices, forecasting an average price reduction of 9% for generic drugs in the United States by the end of 2017.
Tao Jianhong stressed that CDE published the first batch of patent expiration has not yet generic drugs catalog, in stimulating the vitality of innovation at the same time, the domestic suitable drug companies can be used as a reference.
9. The biosimilar market is in the ascendant, with China leading in the number of products under research
There are currently nearly 850 biosimilars in development or sale worldwide, of which about 125 are in clinical trials. There are more than 515 improved biosimilars in development or sale, with more than 200 in clinical trials. In about five years, biosimilars will overtake other innovative products. On the one hand, it reflects the huge market demand in China, but also reflects the fierce competition in China\'s biosimilar drugs.
In the world, 80% of the indications for biosimilars under research are autoimmune diseases and tumor-related diseases, both in China and globally, monoclonal antibody accounts for the highest proportion of biosimilars under research, reaching 40.7% in China. At present, many domestic pharmaceutical companies are in the layout of biosimilar drugs. According to Thomson Reuters, in 2016, the number of Suzhou Kangning Jerry in the development of biosimilar drugs has reached 28, followed by Qilu Pharmaceutical in the development of biosimilar drugs the number also reached 10.
The six Mabs in the Top10 global drug sales in 2016 were: Bevacizumab, Adalimumab, trastuzumab, rituximab, Infliximab and Etanercept. Its patents are about to expire in the European Union and the United States (some patents expired in 2015 and 2017 in the European Union). At present, these 6 MAB have been under research enterprises in China, including 14 bevacizumab analogues, 15 Adalimumab analogues, 13 trastuzumab analogues, 6 rituximab analogues, 3 infliximab analogues, and 7 Etanercprimab analogues.
10. Orphan drug research and development meets the clinical value orientation, and China\'s rare disease drug use ushered in a favorable policy
At present, there are more than 6,000 rare diseases in the world, and only more than 400 orphan drugs have been approved, and the gap of rare disease drugs is large. Tao Jianhong analysis said that the development of orphan drugs has its own advantages, one is the need for fewer patients, many can be listed after the completion of the second phase of clinical. Second, the success rate of orphan drug development is three times higher than that of general drug development. Third, the low cost of commercial promotion after listing, coupled with 7-10 years of exclusivity, so that other generic drug manufacturers can not follow. Fourth, orphan drugs can expand new indications after the market, great commercial value, easy to become blockbuster products.
According to the budget, global orphan drug sales will total $209 billion in 2022. In 2017, China will also accelerate the development and listing of orphan drugs by issuing a list of rare diseases, prioritizing review and approval, conditionally allowing overseas new drugs to be listed, and medical insurance access. The opening of orphan drugs will be an area worthy of attention for domestic companies.
Summary: Pharmaceutical innovation enters the golden age
After sorting out the ten features of the global pharmaceutical innovation ecology, Tao Jianhong pointed out that China\'s pharmaceutical innovation is entering the golden age, which includes:
With the future population aging, residential urbanization, people\'s health awareness and the change of disease spectrum, the demand for medicine will continue to grow. The next 5-10 years is a critical period for the development of medicine and a promising period of strategic opportunities.
In the future, pharmaceutical research and development will further restructure the value chain and allocate resources globally. From laboratory to clinical research, from pharmaceutical companies to R&D outsourcing, from capital incubation to listing, it is necessary to form a multi-party integration of innovation ecosystem. Therefore, the "buy doctrine" of new drugs is back in vogue, and large-scale mergers and acquisitions expand the R&D pipeline.
In view of the characteristics of generic drugs, "breakthrough" generic drugs to accelerate the listing process, biosimilar large varieties of the market is on the rise, the Chinese market through the "quality and efficacy consistency" of generic drugs will become the mainstream.
China\'s accession to ICH will open a new pattern of global research and development, research and development investment will continue to increase, domestic and foreign drug approval will speed up, and new drugs will be launched to meet clinical needs.
The rise of small and medium-sized biopharmaceutical companies has led some large pharmaceutical companies to adjust the traditional early research and development model and cooperate with companies focused on research and development. Compared with the international mainstream, the gap and challenge still exist, China will usher in the second import drug boom, the market competition will become increasingly fierce, import substitution, beyond the competition of the new model will be born, grow and mature in the competition.
2. Focus on three major categories of clinical value
1. Anti-tumor drugs: immunotherapy is emerging
The global oncology drug market is estimated to reach $150 billion, and the annual growth rate of oncology drug spending is forecast to be 7.5-10.5% through 2020. From the perspective of anti-tumor market in different regions of the world, the United States is the largest, followed by the European Union and Japan, and emerging markets including China remain year by year