Fierce competition in the year of the outbreak of bio similar drugs

[foreword] monoclonal antibody is a highly uniform antibody produced by a single B cell clone, which only targets a specific epitope Because of its high purity and specificity, monoclonal antibodies can accurately identify the subtle differences of antigen substances, and can combine with certain antigen specificity It has the characteristics of no damage to normal cells, less dosage, high efficacy and little side effects The combination of drugs and biological macromolecules is the drug target The discovery of new drug target is the breakthrough of new drug research and development Therefore, monoclonal antibody drugs have become one of the fastest growing fields in the pharmaceutical industry and one of the most profitable varieties in the global biomedical technology market According to frost Sullivan report, monoclonal antibodies have been one of the largest categories in the global biopharmaceutical market since 2013 In 2018, the global monoclonal antibody market segment accounted for 55.3% of the global bio drug market, with a compound annual growth rate of 13.2% from 2014 to 2018 There are more than 20 monoclonal antibody drugs with sales over US $1 billion in the world, among which the top 10 are: China's monoclonal antibody drug market is in a period of rapid development Although many drugs listed in European and American markets have not been approved in China, in recent years, the State Drug Administration has accelerated the process of drug R & D approval At present, seven domestic monoclonal antibody varieties have been approved for listing in China At the same time, since 2017, the national medical insurance procurement has significantly expanded the coverage of McAbs, which is conducive to improving the penetration rate of McAbs in the future and further promoting the expansion of China's McAb market The core patent of adamumumab, the star product, expired in China in 2016 The first adamumumab bioequivalent drug, gelolide, produced by biotherapex, was approved for marketing in China on November 7, 2019 Because the research and development of bioequivalent drugs is lower than that of the original drugs, it has obvious price advantage At present, domestic enterprises, such as Xinda biology, Haizheng pharmaceutical, Fuhong Hanlin, etc., are waiting for approval of similar adamumumab biological drugs The penetration rate of adamumumab in the Chinese market will increase rapidly, and the market scale is expected to increase rapidly As a broad-spectrum anti-tumor monoclonal antibody, PD-1 / PD-L1, as of June 2019, 9 products have been approved globally, including 6 PD-1 and 3 PD-L1 products Bristol Myers Squibb's navulizumab and mosadon's pabolizumab were approved in the United States as early as 2014 At present, they have been approved for the treatment of various indications including melanoma, non-small cell lung cancer, renal cell cancer, Hodgkin's lymphoma, head and neck cancer, urothelial cancer, colorectal cancer, liver cell cancer, etc As of June 2019, tuoyi of Junshi biology, dabushu of Cinda biology and Erica of Hengrui medicine have passed the listing approval application of the State Drug Administration The first PCSK9 (a liver derived secretory protein) inhibitor new drug to be listed in China, iluoyuzumab, developed by Amgen, was approved by the State Drug Administration in July 2018 for the treatment of adult or adolescent homozygous familial hypercholesterolemia and adult atherosclerotic cardiovascular disease, and for the reduction of myocardial infarction Risk of stroke and coronary revascularization 1 High technical barriers Monoclonal antibody medicine is a high input and high-yield industry The production technology is mainly flow culture and continuous perfusion culture Due to the long-term technical blockade of foreign enterprises, the large-scale production technology of monoclonal antibody in China lags behind that of foreign countries, and it is difficult to realize industrialization However, according to Xinda biological's annual report, the company has three sets of 1000 liter bioreactors for the production of Dabusu ® (cindilimab injection), and the second production facility of six sets of 3000 liter stainless steel bioreactors has completed the commissioning and validation of GMP, with a total capacity of 21000 liters at present 2 Large R & D investment The structure of biological drugs is generally more complex than chemical drugs Biological innovative drugs need 10 to 15 years of R & D and clinical trials It is difficult to develop with a long R & D cycle and a long return cycle Even biological similar drugs need huge investment According to Xinda biological's 2018 annual report, the R & D expenditure in 2018 is more than 1.2 billion yuan, and there are 19 products under research And PD-1 product dabeshu was approved to be listed in the Chinese market on March 8, 2019, with a sales revenue of 331 million yuan as of June 30, 2019 3 Fierce product competition