First, targeted drugs open a new era of tumor treatment
Targeted drugs have high specificity and little toxic and side effects, and have obvious curative effects on various malignant tumors. In recent ten years, they have become the mainstream of new anti-tumor drugs.
1997 FDA approved the first tumor-targeted drug: rituximab, which opened a new era of tumor treatment; 1997-2005, a few targeted monoclonal antibodies of small molecules and large molecules went on the market, and targeted drugs developed rapidly. From 2005 to 20 17, the proportion of targeted drugs increased year by year. 14 antineoplastic drugs approved by 20 15, 12 is a targeted drug, and both of them are targeted drugs approved by 20 16 and 20 17.
Figure11997-2017 Number and types of cancer drugs approved by FDA.
Source: Forestry Bureau, created and sorted by Flint.
2. Targeted drugs refer to drugs or their preparations endowed with targeting ability.
Targeted drugs are the product of the integration and development of biotechnology and information technology. The rapid progress of pharmacy, molecular biology and bioinformatics has promoted the human genome project, and the rapid development of functional genomics in the post-genome era has strongly promoted the identification of targets and the development of structural biology, and promoted the precise drug design based on the three-dimensional structure of targets.
Rituximab (anti-CD20 monoclonal antibody) is the first monoclonal antibody targeted drug approved for the treatment of tumors during the period of 1997+0 1 month. From 200 1 to 10, imatinib mesylate (tyrosine kinase inhibitor) became the first small molecule targeted drug approved to treat tumors.
Targeted drugs can be applied to specific lesion sites to reduce the damage to normal tissues and cells, and are mainly used for cancer treatment. Different from the traditional carpet bombing of chemotherapy and radiotherapy, the target is unclear, and tumor cells and normal human cells are defeated. Targeted therapy is like a precision guided cruise missile, which is targeted and can accurately hit the cancerous site. This drug is endowed with targeting, which can accumulate or release effective components at the target site for a specific lesion, and form a relatively high concentration at the target site, thus improving the drug effect, inhibiting toxic and side effects and reducing the damage to normal tissues and cells. According to the different targeting mechanisms, targeted drugs can be divided into three categories: passive targeting, active targeting and physical targeting. According to different targeting levels, targeted drugs can be divided into three categories: tissue and organ level, cellular level and subcellular level.
Fig. 2 Classification of targeted drugs
Image source: flint creation
Third, targeted drugs promote the rapid growth of the global anti-tumor drug market.
The global anticancer drug market is large, and the growth rate is much higher than the average level of the pharmaceutical industry market. The report "Global Cancer Trends in 20 18" shows that in 20 17, the global cost of cancer treatment and adjuvant therapy was as high as13.3 billion US dollars, up about 12.5% year-on-year. The United States, Japan and five European countries (Germany, Britain, France, Italy and Spain) account for 74% of the global treatment expenditure, of which the United States accounts for 46%, and the total cost of anti-cancer treatment and adjuvant treatment is about $6,654.38 billion. With the improvement of medical quality requirements in developing countries, the global anticancer drug market is expected to grow to18-200 billion US dollars in the next five years.
Figure 3 Global cancer treatment and adjuvant treatment costs
Source: Global Oncology Trend 20 18.
Targeted drugs have a significant therapeutic effect on tumors because of their small side effects and high specificity. They are praised by the medical community as the most promising drugs to "conquer" cancer and become the mainstream of new anti-tumor drugs in recent years. Judging from the types of anticancer drugs, targeted drugs account for half of the country. According to statistics, during the period of 1997-20 17, 14 1 antineoplastic drugs (excluding adjuvant drugs) were approved by FDA, including 35 biological products (including 2 ADCs) and chemical drugs/kloc.
Fig. 41997-2017 classification of anticancer drugs approved by FDA.
Source: State Administration of Medical Products.
In 20 17, all the anti-tumor drugs ranked first in the world 10 were targeted drugs, including 6 kinds of macromolecular targeted anti-tumor drugs (monoclonal antibodies and cytokines) and 4 kinds of small molecular targeted anti-tumor drugs. 20 17 years ago 10, the total sales of drugs was * * * 54.09 billion USD, up by 33.4% over the previous year, accounting for 2,065,438+.
In 20 17, the global sales of TOP 10 tumor drugs totaled 52.252 billion dollars, including 9 kinds of targeted drugs, with sales of 477.1800 million dollars, accounting for 9 1.32%. Lenalidomide, a small molecule drug, has maintained rapid growth in the past few years, and 20 17 has surpassed rituximab to become the first-selling anti-tumor drug. Roche Three Musketeers: Rituximab, Bevacizumab and Tratuzumab occupy 2-4 positions; As the representative of immunotherapy, the BMS monoclonal antibody Navumab PD- 1 4 listed on 20 14 and Pamzumab of Merck ranked fifth and eighth respectively. In the future, as the patents of rituximab and bevacizumab expire, these two drugs will be withdrawn from the list with a high probability. PD- 1 monoclonal antibody drugs Navumab, Pamuzumab and CDK inhibitor PaBosini are expected to shoulder the banner of tumor drug market and become new representative varieties.
Table 1 20 17 Top 10 tumor drugs in the world (unit: billion US dollars)
Source: State Administration of Medical Products.
Four, China's targeted drug therapy started late, and the future growth space is broad.
China is a country with high incidence of cancer, and the number of cases continues to increase year by year. Cancer is the first cause of death among Chinese residents. In 20 17, the proportion of urban residents in China who died of malignant tumors was 26%, which was the first cause of death. The death rate of rural residents from malignant tumors is 23%, second only to the death rate of heart disease. Based on this, the tumor treatment market in China is expanding. According to public data, the market size of anticancer drugs in China reached126.8 billion yuan in 20 1268, an increase of 14.27% over the previous year. It is estimated that the compound annual growth rate of the anticancer drug market will be 12.30% in the future, and the scale of the anticancer drug market in China will be as high as 200 billion yuan. 38637.8888888886 1
Figure 5 Proportion of main causes of death among residents in 2017 years
(Outer circle: countryside, inner circle: city)
Source: Ping An Securities
Fig. 6 Market size of antineoplastic drugs in China from 2010 to 2022.
Source: Ping An Securities
In 2005, gefitinib developed by AstraZeneca became the first targeted drug to enter the China market. 20 1 1, ectinib developed by Beida Pharmaceutical was approved, becoming the first small molecule targeted anticancer drug with independent intellectual property rights in China. From 2065438 to 2008, the independently developed furoquintini by Hutchison Whampoa Medicine went on the market, becoming the first mainstream anticancer drug in China from research and development to application for new drug listing. Target pharmaceutical companies represented by Beida Pharmaceutical, Hengrui Pharma and Zheng Da Tianqing are concentrated in Jiangsu and Shanghai. The research and development of targeted drugs mainly depends on large pharmaceutical companies in the southeast coast.
Fig. 7 Distribution of some target drug enterprises in China
Source: Flint's creation
Figure 8 Distribution of scientific research units of targeted drugs in China.
Source: Flint's creation
By the end of 20 17, CFDA*** had approved the listing of 60 anti-tumor drugs (excluding adjuvant drugs)/kloc-0, including 20 chemical drugs/kloc-0 and 40 biological products; There are only 37 targeted drugs, 8 of which are domestic targeted drugs. Among more than 90 targeted drugs approved by FDA, only 1/3 is listed in China, and there are still few new anticancer drugs available for cancer patients in China.
However, with the acceleration of registration approval and the implementation of a series of policies to encourage imported anticancer drugs to be listed in China, the approval speed in 20 18 was obviously accelerated, and nine new targeted anticancer drugs were approved for listing. In recent two years, innovative targeted anti-tumor drugs have been included in the "priority approval" list of CDE. 20 15-20 18 in the third quarter, there were 1 17 applications for the production or clinical use of tinib drugs alone, and a large number of targeted drugs will be listed in China in the next few years.
Table 2 Innovative original drug information of tumor-targeted drugs in China
Source: Flint creation is organized according to public information.
Predict the future market of targeted drugs with verb (abbreviation of verb)
1. Tumor-targeted drugs are the focus of global research and development.
According to IMS Health's report, the global cancer drug market has greatly increased from $83.2 billion in 20 15 to $43.5 billion in 20 19, with a compound annual growth rate of 14.6%, accounting for 7.5% and10, respectively. It is predicted that by 2020, the global cancer drug market will exceed $654.38+05 billion, an increase of nearly 50% compared with $83.2 billion in 2065.438+05.
At present, there is a huge market of hundreds of billions of dollars for tumor drugs in the world, among which targeted anti-tumor drugs account for nearly 50%. In 2005, the compound growth rate of 201-2018% was significantly higher than that of hormone tumor drugs (6% in 5 years) and cytotoxic tumor drugs (3% in 5 years). In 20 1 1-20 16 years, 68 new anti-tumor drugs were approved for marketing, and targeted drugs accounted for more than 80%. In 20 16, 63 1 cancer drug research projects are in clinical phase II/III, of which nearly 90% are targeted drugs, and the proportion of targeted biological drugs has increased from 2 1% in 2006 to 43% in 20 16, which is expected to become the main force of cancer drugs in the future. In 20 15 years, among the best-selling 10 tumor drugs in the world, 9 were targeted drugs, with total sales reaching 42 billion dollars. With the approval of subsequent targeted drugs, the proportion of targeted drugs is expected to continue to rise in the future.
Fig. 9 Global tumor drug market forecast in 2010-2020 (USD 100 million)
Data source: Flint creation is organized according to public information.
2. Keep up with hot spots and catch up: domestic targeted anticancer drugs are full of stamina.
The rapid growth of the market has prompted more and more domestic listed pharmaceutical companies to join the research and development of innovative anti-tumor drugs. Among A-share listed companies, Hengrui Pharma, Fosun Pharma, Livzon Group, Beida Pharmaceuticals and many other companies all have layouts in the field of cancer. Although it entered the research and development late, it followed the hot spots and focused on the field of targeted anti-tumor drugs, that is, targeted small molecules and monoclonal antibodies, fusion proteins and other biological products. At present, CFDA has approved 8 domestic 1 targeted anticancer drugs, of which 6 are targeted small molecule anticancer drugs and 2 are biomacromolecules, and most of them have achieved good sales performance.
The approval time is shortened. For a long time, the evaluation time of new drugs in China is long, with an average of 63 months from clinical application to listing, far exceeding the average approval time of the United States 10 month. Since 20 15, in order to speed up the review and approval and meet the needs of clinical drugs, a priority review and approval system has been gradually established on the basis of the original special approval channel for drug registration, and innovative drugs that have not been listed at home and abroad, overseas original drugs that have not been listed in China, and new drugs that have been included in major special projects, and new drugs that prevent and treat AIDS and other major diseases have been included in the priority review channel, encouraging research and development of innovative drugs that meet clinical needs.
Medical insurance policy support. From August, 2065438 to August, 2009, the new national medical insurance drug list was released, focusing on supporting innovative drugs and drugs for serious diseases (such as cancer, diabetes, cardiovascular and cerebrovascular diseases, etc. ) and children's drugs. 97 kinds of negotiated drugs were all included in the scope of Class B drugs in the medical insurance catalogue, with an average price reduction of 60%, involving tumors, rare diseases, chronic diseases, children's drugs, etc. 10 more clinical treatment fields. The policy is conducive to the research and development and market expansion of cancer drugs, and the favorable policies for cancer drugs will continue in the future, or involve supporting approval, market access, medical insurance reimbursement and so on.
Domestic leading enterprises have great potential. There is an obvious generation gap in the domestic and international markets of tumor-targeted drugs, and the competition in the field of tumor-targeted drugs is low, so the domestic leading enterprises have great potential. There is a big gap between the efficiency of new drug approval in China and that in Europe and America. At present, there are 9 anti-tumor targeting micromolecules 19 (three of which are original products from China) and 6 anti-tumor monoclonal antibodies (two of which are original products) listed in China, of which nearly 60% are overseas varieties listed 20 10 years ago, and nearly 85% of the market share is occupied by foreign companies. The distribution of targeted drugs in tumor-prone areas will be the core of future enterprise competition. At present, small molecule targeted drugs for lung cancer in China are mainly the first batch of drugs to replace Nitinol. The small molecular targeted drugs for breast cancer, liver cancer and gastric cancer are rapatinib, sorafenib and apatinib, and there is no indication for colorectal cancer, among which only apatinib belongs to the original research products of domestic enterprises. The domestic monoclonal antibody field is in the introduction period, and most of the market share is occupied by Roche. Domestic enterprises only have Chengdu Huashen's iodine [13 1I] metuximab for liver cancer and nimotuzumab's Baitai biotherapy for nasopharyngeal cancer. PD- 1/PD-L 1 monoclonal antibodies and ADC drugs for tumor immunotherapy have not been listed in China at present.
Cytotoxic drugs are still the mainstream of tumor drugs market in China. Targeted drugs occupy nearly 75% of the market in developed countries such as the United States, but cytotoxic drugs represented by antimetabolic drugs, botanical drugs and alkylating agents are still the mainstream (nearly 50%) in the domestic tumor drug market, and may still occupy a dominant position in the future. First of all, traditional anti-tumor drugs have many varieties and broad anti-tumor spectrum, and they are still the first choice for first-line anti-tumor treatment; Secondly, traditional cancer drugs are cheaper than targeted drugs, and most of them enter national medical insurance or local medical insurance in most provinces and cities. 20 12 new edition of essential drugs is included in anticancer drugs for the first time, all of which are traditional anticancer drugs. In 20 16 years, among the top ten varieties of tumor drugs sold in sample hospitals, seven were cytotoxic drugs.
The proportion of targeted drugs in China cancer market will increase year by year. The domestic anticancer drug market is undergoing product upgrade. Since 2005, the sales proportion of traditional botanical drugs and alkylating agents has been decreasing year by year. The proportion of targeted small molecules increased from 2.0% in 2005 to 8.9% in 20 16 years, and the proportion of monoclonal antibodies increased from 3.9% in 2005 to 12.6% in 20 16 years. According to the statistics of Zhiyan Data Research Center, the anti-tumor market in China was about 83.7 billion in 20 14, with a compound growth rate of nearly 20% from 20 10 to 20 14. Assuming that low-priced drugs such as cytotoxic drugs are still the main drugs for cancer, it is estimated that the market size of cancer drugs in China will reach 654.38+000 billion yuan by 2020. According to the proportion of targeted drugs in Europe and America, the target market capacity of targeted drugs in China will reach 40-50 billion yuan.