Analysis of competition pattern of domestic microsphere / liposome research and development enterprises

Abstract: for the pharmaceutical companies that have already launched microspheres / lipid system products, such as Lizhu group, Beijing Bonte, LVYE pharmaceutical, Shiyao group, Beijing Taide, Fudan Zhangjiang, Changzhou Jinyuan, Shanghai Shangxin, etc., they have accumulated rich experience in the industrialization area, at the same time, they have a layout in sales and have strong market competitiveness Overview of microsphere research and development enterprises in China main enterprises in microsphere field are Lizhu group, Bonte pharmaceutical and LVYE pharmaceutical, etc The listed variety of Lizhu group is leuprorelin microsphere, one of which has been approved in clinical research, one of which has been reviewed and approved, four of which have been studied in preclinical research, and there are many research pipelines in research Bonte Pharmaceutical Co., Ltd has listed the first domestic imitated leuprorelin acetate sustained-release microsphere for injection, and has rich experience in the research, development and production of microsphere preparation; LVYE pharmaceutical entered three microsphere varieties declared in the United States by 505 (b) (2), among which risperidone sustained-release microsphere for injection has entered the new drug application stage There are 5 research projects of sustained-release microspheres in China, among which goserellin acetate sustained-release microspheres and rotigotine sustained-release microspheres for injection have entered phase III clinical practice Overview of domestic research and development enterprises of liposome preparations the main enterprises in the field of liposomes are Shiyao group, LVYE pharmaceutical, Changzhou Jinyuan pharmaceutical, Beijing Taide, etc Vincristine sulfate liposome of green leaf pharmaceutical has entered the third stage of clinical application in China The quality advantage of doxorubicin hydrochloride liposome (domenicol) is obvious, with market share of 60% in 2017 Another three lipid system agents have entered clinical trials Beijing Taide has one liposomal in research phase I clinical trial; Changzhou Jinyuan listed liposomal formulation is doxorubicin hydrochloride liposomal (Lixing), and another three liposomals have entered the clinical trial For the pharmaceutical enterprises in the research and development stage, because the microsphere liposome in China is still in the initial stage, many products are imported, and there are few domestic products The R & D pharmaceutical enterprises with the R & D strength of microsphere, liposome, lipid microsphere, nanoparticles and other innovative preparations have great potential in these drugs, such as shengzhao pharmaceutical, LVYE pharmaceutical, etc.; therefore, they are rich in research pipeline and research R & D enterprises with strong development ability and better product quality will also have a place in the market competition of microspheres and liposomes in the future Lizhu group is a comprehensive enterprise group integrating research and development, production and sales of medicine The company was founded in 1985 At present, the company's products include several advantageous fields, such as assisted reproduction, gastrointestinal medicine and tumor assistance, with more than 400 product reserves It is leading in domestic technology of macromolecular biological medicine and microsphere innovative medicine The company is one of the only two manufacturers (Shanghai Lizhu Pharmaceutical Co., Ltd and Beijing Bonte Pharmaceutical Co., Ltd.) of microsphere injection preparation (excluding contrast agent) in China, with the largest market share in domestic varieties Leuprorelin acetate microspheres for injection were approved for marketing in August 2009 Due to its high technical barriers and increasingly strict evaluation conditions, there are no other microspheres in China With its nationwide sales network and professional academic promotion ability, the market share of leuprorelin microspheres has been expanding, from 27.6% in 2014 to 35.9% in 2017, with sales volume of 644 million yuan in 2017 It is estimated that the corresponding market value of leuprorelin microspheres products of Lizhu group can reach 3.2-4 billion yuan (the net sales interest rate of general innovative products can reach 20% - 25%, and this product will be given 25 times of PE); in addition to the listed leuprorelin microspheres, the microsphere products under research of the company also include triptorelin, octreotide and other microsphere products that have been listed in the world, with rich pipeline under research Table 1 data source of microsphere series products of Lizhu group: Pharmaceutical intelligence data 2 Shengzhao pharmaceutical is a high-tech enterprise focusing on the research and development of innovative preparations, with four major innovative preparation research and development platforms The company was founded in 2011 and listed on the new third board in 2015 In January 2017, the company's "shengzhao injection long-term sustained-release and targeted preparation provincial high-tech enterprise research and development center" was recognized as the provincial high-tech enterprise research and development center of Zhejiang Province in 2016 The company is committed to creating an innovative pharmaceutical platform with a stable core R & D team At present, there are only 3 domestic enterprises applying for registration of microsphere preparation products in CFDA, and the company has gathered the microsphere technical directors of two of them, with strong scientific research strength At the same time, the company has four major innovative preparation R & D platforms, including microsphere, liposome, lipid microsphere and nanoparticles The indications of technical products cover endocrine system, malignant tumor system, cardiovascular system and spirit Spectrum of four major diseases of nervous system R & D ability of innovative preparations is strong Shengzhao has rich experience in drug R & D: Dr Huang Huifeng, technical director of the company's targeted drug research center, has rich development experience From July 2009 to November 2012, Dr Jiang Chaojun, technical director of long-term sustained-release preparation research center, served as the director of microsphere preparation room of Drug Research Institute of Qilu Pharmaceutical Co., Ltd.; since February 2013, he has served as technical director of long-term sustained-release preparation research center of the company The company's R & D director has rich experience and the product can be put on the market The company's product quality and process level are at the forefront of the industry, and the pipeline research is rich Due to the leading technology of auxiliary equipment and technology, the company has a strong advantage in the quality of innovative pharmaceutical products The larger the production scale of the dosage form product is, the more mature the technology is The production scale of several microsphere manufacturers in China is less than 300g, while the production scale of shengzhao microsphere can be linearly enlarged to kilogram level According to the public data, the purity of risperidone microspheres is 99.95%, superior to the original research product (99.8%) and more than other domestic competitors; the purity of exenatide microspheres is 99%, reaching the world-class level; the research on olanzapine long-acting preparation and shengzhao process is comprehensive and stable, the registration data conforms to the EU standard, and the document quality is high As of June 30, 2018, the company has 16 innovative preparations under research, including 12 long-term sustained-release preparations and 4 targeted preparations The progress of each project is as follows: Table 2 information source of shengzhao pharmaceutical pipeline under research: semiannual report of shengzhao pharmaceutical in 2018 3 Beijing Bonte Pharmaceutical Co., Ltd is a high-tech enterprise focusing on the research and development and production of microsphere preparations The company was founded in 2004 and registered in Changping Park of Zhongguancun High Tech Park It is a high-tech enterprise certified by Beijing Municipal Science and Technology Commission It has passed GMP certification of the State Food and drug administration, research and development and production certification of microsphere drugs of Beijing Municipal Drug Administration The company has established an industrial platform for microsphere drug (including microsphere solvent) production and a research and development platform for microsphere drug preparation technology It has rich experience in the research and development and production of microsphere preparation In the research and development of polypeptide microsphere drug and industrial technology, it has applied for 9 national invention patents, 5 authorized invention patents and 2 in the process of examination In 2009, the company successfully developed the first generic drug microsphere in China - bonnocon (leuprorelin acetate sustained-release microsphere for injection), which was approved by the State Food and Drug Administration and successfully listed on the market This product broke the situation that the production of drug microspheres was monopolized by Europe, America and Japan for nearly 30 years, and filled in the blank of no domestic microsphere preparation for injection in China In the past five years, the market share of microsphere preparation has increased steadily, and it has continuously replaced the imported microsphere preparation In 2017, the sales volume of the product was 620 million yuan It is estimated that the corresponding market value of leuprorelin microsphere product of Beijing Bonte can reach 3.1-3.9 billion yuan (the sales net interest rate of general innovative preparation product can reach 20% - 25%, and the product will be valued at 25 times of PE) 4 LVYE pharmaceutical is an international pharmaceutical company committed to the research, development, production and sales of innovative drugs The company was founded in 1994 and listed in Hong Kong stock market in 2014 The company has R & D centers in China, the United States and Europe, and branches in Hong Kong, Singapore and Malaysia The company has more than 30 drugs under research in China and more than 10 drugs under research overseas, and has 7 production bases and more than 30 production lines in the world, and has established GMP quality management and control system in line with international standards LVYE pharmaceutical now has more than 140 approved products on the market, covering the largest and fastest-growing treatment fields such as anti-tumor, central nervous system, cardiovascular, digestion and metabolism; its business covers more than 80 countries and regions around the world, including major global pharmaceutical markets such as China, the United States, Europe, Japan, and fast-growing international emerging markets The company owns the world's first paclitaxel liposome, accounting for more than 70% of the liposome market share In 2003, the company developed the world's first paclitaxel liposome, which replaced castor oil, the original vehicle of paclitaxel, with phospholipid to avoid the hypersensitive reaction caused by castor oil and effectively reduce the drug toxicity Since its listing in 2003, the market share has increased year by year In 2017, the sales volume was 3.11 billion yuan, with an annual growth rate of about 20% in recent years The production of paclitaxel liposomes of green leaf pharmaceutical was estimated The corresponding market value of the product can reach 15.5-19.5 billion yuan (the sales net interest rate of general innovative pharmaceutical products can reach 20% - 25%, and the product is given a 25 times PE valuation) The company's microsphere liposome and other advanced drug delivery technologies have reached the international leading level, with rich pipeline in research at home and abroad, and rapid clinical progress The company has established three advanced drug delivery technologies, including liposome and targeted drug delivery technology, transdermal drug delivery, long-term and sustained-release technology, among which microsphere, liposome and other technologies have reached the international leading level Relying on the corresponding technology platform, the company has arranged a number of products at home and abroad The drugs distributed overseas include risperidone sustained-release microspheres for injection, rotigotine sustained-release microspheres for injection and goserellin sustained-release microspheres for injection, which are declared by 505 (b) (2), among which risperidone sustained-release microspheres for injection have entered the new drug application stage There are also a lot of research products in China, including four sustained-release microspheres and one liposome, among which vincristine sulfate liposome, goserellin acetate sustained-release microspheres for injection and rotigotine sustained-release microspheres for injection have entered the third phase of clinical practice Table 3 clinical pipeline data sources of GLP at home and abroad: Pharmaceutical intelligence data 5 Shiyao group is one of the leading enterprises in China's pharmaceutical industry Founded in 1997, after more than 20 years of development, the group has gradually transformed from the most important API manufacturer in China into an innovative pharmaceutical enterprise dominated by innovative brand drugs The group was listed in Hong Kong as a whole in 2012 and is a component of Hong Kong Hang Seng Index Shiyao group is mainly engaged in the development, production and sales of pharmaceutical products Its products mainly include seven series of nearly 1000 varieties, including cardio cerebrovascular, antibiotics, vitamins, antipyretic and analgesic, digestive system drugs, anti-tumor drugs, etc., with 30 single varieties selling more than 100 million yuan, and the products are sold all over the country and more than 60 countries and regions in the world Doxorubicin hydrochloride liposome injection entered the local supplementary medical insurance category B drug catalog of Hebei and Xinjiang in 2017; the sales volume of doxorubicin hydrochloride liposome injection in 2017 was 610 million yuan, and the corresponding market value of the product of Shiyao group was estimated to be 3-3.8 billion yuan (the sales net interest rate of general innovative product can be 20% - 25%, and the product will be valued at 25 times P / E) In addition to the listed drug domenicol, there are many drugs under research in the aspect of liposomes, including