The five-year compound growth rate is 9.2%! What are the opportunities in the natural anti-tumor drug market?
June 10, 2021
一. Basic information of taxane anti-tumor drugs
Product description
Paclitaxel (Paclitaxel, PTX) is a microtubule stabilizing drug that selectively inhibits the depolymerization of microtubules, thereby arresting mitosis and leading to cell death. It is a highly effective, low-toxic, and broad-spectrum anti-tumor drug that is widely used in clinical practice. It is used in ovarian cancer, breast cancer, lung cancer, head and neck cancer, esophageal cancer, gastric cancer and soft tissue sarcoma. Paclitaxel, as a diterpene alkaloid compound with anti-cancer activity, its novel chemical structure, extensive and significant biological activity, and a new and unique mechanism of action make it popular among botanists, chemists, pharmacologists, and molecular The great favor of biologists has made it a world-renowned anti-cancer star and research focus in the second half of the 20th century. Although paclitaxel has good anti-cancer activity, due to its poor water solubility, traditional dosage forms use hydrogenated castor oil and absolute ethanol as carriers. Hydrogenated castor oil can cause serious adverse reactions such as allergies, nephrotoxicity and neurotoxicity, which limits its clinical practice. application. In order to overcome the limitations of these adverse reactions, paclitaxel liposomes and paclitaxel albumin-binding types have been developed successively. The development of paclitaxel derivatives such as docetaxel (docetaxel) and carbachol (cabazitaxel) has sparked an upsurge in the research of taxane anticancer drugs. After investigation, the world's major taxane drugs under development are shown in Table 1-1 and Table 1-2.
R & D history
The discovery of paclitaxel began in 1962, and for nearly 60 years since then, people's enthusiasm for its development has never faded. The upgrade of paclitaxel has three lines: derivative + dosage form upgrade + indication expansion. The related research and development process is shown in the table below.
二. Research status of taxane anti-tumor drugs on the market
Domestic listing in research
The main domestically marketed taxane preparations under research include: paclitaxel preparations, docetaxel preparations, cabazitaxel preparations, larotaxel preparations, xinretaxel preparations, comortaxel preparations and milatazid preparations. See the table below for listing details. Among them, paclitaxel injection enters the medical insurance category A, and docetaxel injection enters the medical insurance category B.
Foreign listing situation
The main foreign taxane preparations on the market include: paclitaxel preparations, docetaxel preparations and cabazitaxel preparations. See the table below for details.
三. Competitive products and competitive landscape
Antitumor drugs
As a broad-spectrum cytotoxic drug, taxane anti-tumor drugs are widely used in various tumors, and are used as first-line drugs in a variety of tumor chemotherapy principles. Tumor treatment methods are mainly divided into 4 types, including traditional therapies, targeted therapies, immunotherapy and gene therapy. According to the ATC classification, anti-tumor drugs are mainly divided into the following categories.
Taxanes
At present, the only taxane anti-tumor drugs on the market in the world are paclitaxel, docetaxel and cabazitaxel, and the taxane anti-tumor drugs that are under development and entering phase III clinical trials include tercetaxel, lalotaxel and Travatide paclitaxel. The taxane anti-tumor drugs under development in China include cabazitaxel, larotazid, xinlitaxel, comtaxel and milatazac. (1) Paclitaxel: Stabilizes microtubules by promoting the combination of tubulin dimers and preventing their depolymerization, thereby inhibiting the normal dynamic reorganization of microtubules that are essential for cell function in the intermittent and mitotic phases , Hinder the replication of tumor cells, so that cancer cells can not continue to divide and die. In addition, paclitaxel also has a radiosensitizing effect, which can promote cell damage caused by ion irradiation. (2) Docetaxel: The mechanism of action is similar to that of paclitaxel. It has a higher affinity to the microtubule binding site, has higher anticancer activity, and has a broader antitumor spectrum than paclitaxel. (3) Cabazitaxel: The mechanism of action is similar to docetaxel. The FDA currently only approves it for use in metastatic castration-resistant prostate cancer where docetaxel is ineffective.
Paclitaxel preparations
Paclitaxel injection, paclitaxel liposomes, and paclitaxel albumin-bound three drugs gradually increase their efficacy, and gradually reduce the incidence and severity of adverse reactions; paclitaxel micelles for injection are adapted by virtue of their advantages in drug loading and tolerable dose It has more potential in disease development. (1) Paclitaxel injection: As the first paclitaxel preparation, Taxol® has achieved great success in the market, but the drug has a very obvious defect: Paclitaxel itself is difficult to dissolve in water, in order to make an injection, the original drug and Other conventional generic drugs have to add the surfactant polyoxyethylene castor oil to the drug. This allergen can stimulate the body to release histamine and cause allergic reactions. Corticosteroids and antihistamines must be pretreated before medication. (2) Paclitaxel liposomes for injection: Lipusu® is the world's first new paclitaxel formulation successfully developed and marketed in response to the clinical defects of Taxol®, and it is also the world's only paclitaxel liposome. Lipusu®'s main excipients are lecithin, cholesterol, and do not contain polyoxyethylene castor oil and ethanol; and it uses special technology to embed the drug in lipid particles with a diameter of micrometer to nanometer, which can make the drug mainly in The liver, spleen, lung and bone marrow are accumulated in tissues and organs, thereby increasing the therapeutic index of the drug, reducing the therapeutic dose of the drug, and reducing the toxicity of the drug, showing a unique advantage in improving patient tolerance. (3) Paclitaxel for injection (albumin-bound type): Abraxane® is the only albumin-bound paclitaxel nanoparticle marketed in the world, and its effectiveness and safety are significantly improved compared to Taxol®. Nanoparticles made of paclitaxel and human albumin by high-pressure vibration technology greatly increase the drug loading of paclitaxel, and at the same time use the properties of human albumin to promote the entry of drugs into tumor cells and increase the efficacy of chemotherapy. (4) Paclitaxel micelles for injection: Samyang has developed CynviloqTM as the world's first paclitaxel micelles to be marketed. This product has a higher tolerated dose than Taxol® and Abraxane®, which means the expansion of indications (pancreatic cancer, bladder cancer, ovarian cancer). At the same time, CynviloqTM uses chemical polymer materials to reduce the risk of microorganisms and immunity. Paclical® developed by Oasmia was launched in Russia in 2015, and its core technology is Oasmia's unique new excipient XR-17. The safety and effectiveness of this product are equivalent to Taxol®, but compared with Taxol®, Abraxane®, and CynviloqTM, its drug loading is greatly increased, and the ratio of excipients to drugs is close to 1:1. In theory, its indication expansion ability is in all The most potential of the drugs on the market.
四. Market situation of taxane anti-tumor drugs
Diseases and market prospects
In 2020, the incidence of various cancers in the world and China is shown in the figure below. Among them, the top three cancers in the world are breast cancer, lung cancer and colorectal cancer, and their incidence accounts for 33.1% of all cancers; the top three cancers in China Lung cancer, colorectal cancer and gastric cancer, the combined incidence of which accounts for 40.6% of all cancers.
Figure 4-1 Proportion of global cancer incidence in 2020
Figure 4-2 Proportions of various types of cancer in China in 2020
Source: WHO: Global Cancer Observatory
The main indications of taxane antitumor drugs are: breast cancer, lung cancer, prostate cancer, gastric cancer, etc., combined with the proportion of various types of cancer, it can be roughly concluded: taxane antitumor drugs can be used in clinical practice in China about 30% Cancer patients.4.2 Global market situation of each category(For the complete report, please consult Yaozhi Consulting)4.3 China's market situation and prospects by category
4.2.1 Anti-tumor drugs.Sample data shows that from 2015 to 2019, the overall market size of China's anti-tumor drugs was US$2.4 to 3.6 billion, with a five-year compound growth rate of 10.2%.Among them, the sales of natural anti-tumor drugs accounted for a relatively stable proportion of 30.3% to 33.4%, and the five-year compound growth rate of sales was 9.2%.
Figure 4-3 Proportion of sales of various anti-tumor drugs in China
Data source: Yaozhi Consulting Co., Ltd.
Taxanes
Sample data shows that from 2015 to 2019, the overall market size of taxane anticancer drugs in China was US$700 to 1 billion, accounting for approximately 27% to 28% of all anticancer drugs, with a five-year compound growth rate of 8.7%. Among them, paclitaxel sales accounted for the largest proportion and increased year by year, from 52.0% in 2015 to 67.5% in 2019, with a five-year compound growth rate of sales of 16.0%. Secondly, the proportion of docetaxel sales fell from 48% in 2015 to 32.5% in 2019, and the five-year compound growth rate of sales was -1.3%. At present, domestic cabazitaxel has entered the phase III clinical stage, and it is expected to be on the market, but combined with its clinical application scope and global market performance, there is no need to worry too much about its impact. However, in recent years, various domestic companies have successively deployed larotasia, xinlitaxi, comotetaxel and milatasa, each of which has certain clinical highlights and advantages, which need to be paid attention to.
Figure 4-4 Proportion of sales of taxane anticancer drugs in China
Data source: Yaozhi Consulting Co., Ltd.
Paclitaxel preparations
The sample data shows that from 2015 to 2019, the sales of paclitaxel liposomes for injection accounted for the largest proportion of the sales of paclitaxel liposomes for injection in China from 2015 to 2019. The sales from 2015 to 2019 remained between 47.3% and 60.7%. , The five-year compound growth rate of sales is 15.3%. Secondly, with the continuous listing of generic drugs in 18 years, the sales of paclitaxel (albumin-bound) for injection in my country has soared from 12.7% in 2018 to 36.2% in 2019, and the five-year compound growth rate of sales is 59.0%. . What needs to be vigilant is that at present, two oral paclitaxel preparations have entered the clinic in China, and the paclitaxel oral solution has entered the phase 3 clinical stage, which is bound to have a significant impact on the future competitive landscape of paclitaxel. In addition, paclitaxel micelles for injection have many domestic companies, and their ability to expand their indications cannot be underestimated. There are many variables in the specific clinical manifestations.
Figure 4-5 Proportion of sales of paclitaxel formulations in China
Data source: Yaozhi Consulting Co., Ltd.
The sample data shows that from 2015 to 2019, among the Chinese paclitaxel preparation brands, Luye Pharma’s Paclitaxel liposome brand "lipusu" accounted for the largest sales volume and increased first and then decreased. Sales from 2015 to 2019 The proportion remained between 47.3% and 60.7%, and the five-year compound growth rate of sales was 15.3%. The original imported paclitaxel (albumin-binding) brand "Abraxane" and the proportion of paclitaxel injection brands have declined to varying degrees. On the other hand, paclitaxel (albumin-binding) generic drug brands (Shipap’s "Kaili" and Hengrui’s "Aiyue") are advancing all the way, and their sales in 2019 accounted for 15.5% and 13.0%, respectively.
Figure 4-6 Proportion of sales of China's paclitaxel brands
Data source: Yaozhi Consulting Co., Ltd.
五, summary
With its novel chemical structure, extensive and significant biological activity, and new and unique mechanism of action, paclitaxel has been greatly favored by botanists, chemists, pharmacologists, molecular biologists, and the market. Thanks to its good safety and effectiveness and low market price, paclitaxel liposomes for injection have always had a good market performance in my country. However, with the successive launch of generic drugs and the selection of centralized procurement, paclitaxel (albumin-bound type), which itself has a greater clinical advantage, is on the rise, and its growth momentum is unstoppable; on the other hand, there are many problems in the old product paclitaxel injection, sales The downward trend seems to be hard to contain anymore. With the continuous entry of paclitaxel imitation companies, especially the impact of paclitaxel (albumin-bound) generic drugs on the entire market in recent years, in the future, the dominance of paclitaxel preparation brands may soon change. . In particular, the export of the original paclitaxel (albumin-binding) brand "Abraxane" has recently been suspended due to unqualified overseas inspections, which is bound to bring more opportunities to the generic drug market.
