Inventory of only 10 domestic McAbs approved by CFDA

In 1986, OKT3, the world's first monoclonal antibody drug for the treatment of rejection in organ transplantation, was approved by the US FDA, which started the development of monoclonal antibody drugs Nowadays, McAb has become an important part of modern biopharmaceutical industry, and it is also the "gold industry" for pharmaceutical enterprises to compete for layout After less than 30 years of rapid development, monoclonal antibodies have made great achievements in the fields of tumor, autoimmune disease, cardiovascular disease and so on With the increase of the number of approved antibody drugs, the scale of antibody market is also expanding In 1997, the global sales of McAbs reached only US $370 million, while in 2007, the sales increased to US $22 billion, and in 2013, the sales reached 62 billion It is understood that there are more than 100 enterprises doing McAb in China In addition to some old brand enterprises such as CITIC Guojian, SAIJIN biological, Baitai biological, Haizheng pharmaceutical, many new enterprises have emerged in recent years, including Lizhu McAb, Xinda biological, Baiji Shenzhou, Jiahe biological, Hengrui pharmaceutical, etc Here is a list of recent events of some related companies: on September 3, Hengrui pharmaceutical announced that the company and Incyte had reached an agreement in the United States to license the project of PD-1 monoclonal antibody (code "shr1210") for tumor immunotherapy with independent intellectual property rights to Incyte in the United States Incyte will be granted the right of exclusive global clinical development and marketing except mainland China, Hong Kong, Macao and Taiwan According to the agreement, Incyte will make a down payment of US $25 million to Hengrui, in addition to US $90 million of listing milestone payment, US $150 million of Clinical Excellence milestone payment and US $530 million of sales performance milestone payment In addition, after the listing of shr1210 abroad, Hengrui will commission from its annual sales according to the agreed proportion On October 12, Xinda biology was likened by people in the industry to a record breaking birth of Xinda biology with a golden spoon The company and Lilly have reached three global development cooperation agreements on bispecific antibody drugs for tumor immunotherapy, with a total milestone payment of more than US $1 billion, becoming the largest amount involved in the international cooperation project of new drugs in China so far Previously, Cinda and Lilly had reached a strategic cooperation agreement on new drug cooperative development, with Lilly providing one variety and Cinda providing two varieties for joint development A down payment of $56 million, including a milestone payment of $400 million for one project The main role of this new cooperation agreement is three new bispecific tumor immunotherapy antibodies, in which Cinda biology will cooperate to lead the development, production and sales of Chinese market, and Lilly will cooperate to lead the development, production and sales of foreign market It is reported that the three antibodies all use the PD-1 monoclonal antibody independently developed by Cinda biology, which is the most promising new bispecific tumor immunotherapy antibody at present Jiahe biology On October 14, Watson bio announced that the McAb products "recombinant anti HER-2 humanized monoclonal antibody for injection (trastuzumab analogues)" and "recombinant anti TNF alpha human mouse chimeric monoclonal antibody for injection (infliximab analogues)" developed by its holding subsidiary Jiahe bio have obtained the clinical approval documents issued by CFDA, and are now carrying out clinical research work In order to accelerate the R & D and industrialization process of the above two monoclonal antibody products, Jiahe biology has established a wholly-owned subsidiary, Yuxi Jiahe Biotechnology Co., Ltd (hereinafter referred to as "Yuxi Jiahe"), which is invested by Yuxi Jiahe as the implementation subject to build the "therapeutic monoclonal antibody drug industrialization project" The construction period of the project is planned to be 2 years, with a total investment of 251149400 yuan It is planned to build a production line with an annual output of 360000 pieces of trastuzumab and 400000 pieces of infliximab, with a total output of 760000 pieces of monoclonal antibody drugs Baiji Shenzhou on June 5, beigene announced that its phase I clinical trial of bgb-a317 for the treatment of advanced tumors has been the first patient Bgb-a317 is a highly selective and powerful all human monoclonal antibody candidate against PD-1 On October 16, Baiji Shenzhou submitted an IPO application to the US Securities and Exchange Commission (SEC) to raise up to US $100 million, and planned to land on the Nasdaq market with bgne as the stock code According to public information, Baiji Shenzhou completed two rounds of financing in November last year and may this year, with prices of 450 million yuan and 600 million yuan respectively If the IPO is successful, it will greatly promote the clinical trial process of Baiji Shenzhou At present, the development market of antibody drugs in China is in a period of rapid development In the past 3-5 years, there have been innovative antibody drugs on the market or entering the late clinical stage in China These breakthrough achievements gradually promote the development of antibody industry in China However, the market scale of domestic monoclonal antibody is still small, and there are few enterprises with mature antibody industry system and large-scale production capacity Due to the late start of the comprehensive research and development of domestic monoclonal antibody and other biological drugs, up to the end of the year, only 10 kinds of domestic monoclonal antibody drugs have been approved by CFDA for listing, accounting for less than half of the total number of domestic monoclonal antibody drugs, and the sales volume only accounts for 1.7% of all biotechnology drugs, far lower than the global 34% level, with a low market share The following table is the domestic monoclonal antibodies approved by CFDA: data source: in the Research Report of Watson biological company (2015-10-15), of the 10 products in China, 4 are mouse derived, 1 chimeric and 2 humanized monoclonal antibodies, and 4 Fc fusion protein drugs, while the proportion of human derived and all humanized monoclonal antibodies in the foreign market is about 90% At present, the only antibody drugs that are really industrialized are yisaipu, jiannipei of Shanghai CITIC Guojian Pharmaceutical Co., Ltd and taixinsheng of Baitai Biological Pharmaceutical Co., Ltd At present, foreign monoclonal antibody is still the leading product in the domestic market, but because of its high price, most patients in China can not afford the treatment of biological drugs such as monoclonal antibody In recent years, more and more domestic enterprises have developed monoclonal antibody products through independent research and development or cooperative development; among them, some enterprises mentioned above have also made outstanding achievements These news are great news for patients in China 1 Anti human T cell CD3 mouse monoclonal antibody for injection manufacturer: Wuhan Institute of Biological Products Co., Ltd gyzz s199900012, approved on September 30, 2010 indications: treatment and prevention of acute rejection in kidney transplantation and organ transplantation patients Pharmacological effect: mouse monoclonal antibody against CD3 antigen of human T lymphocyte has immunosuppressive effect and can reverse the rejection of transplanted organ Its mechanism may be to block the T cell function which plays a major role in the acute allograft rejection The results of in vitro experiments show that the drug can act on CD3 molecules existing on the human T cell membrane and combined with its antigen recognition structure, thus affecting the function of the molecule to transmit activation signals, leading to the release of cytokines, and thus blocking the proliferation and function of the effector cells; the results of in vivo experiments show that the drug can react with most of the T cells in the peripheral blood and tissues, but It has not been found that the drug can react with other blood components or other human tissues 2 Anti human interleukin-8 Monoclonal Antibody Cream (enbok) manufacturer: Dalian Yawei Pharmaceutical Co., Ltd and Dongguan hongyishi Biotechnology Pharmaceutical Co., Ltd on April 17, 2003, CFDA approved the anti human interleukin-8 monoclonal antibody cream of Dongguan hongyishi Biotechnology Pharmaceutical Co., Ltd (gyzz s20010004) On August 30, 2010, CFDA approved the indications of Dalian Yawei Pharmaceutical Co., Ltd anti human interleukin-8 mouse monoclonal antibody cream (gyzz s20030093): for the treatment of psoriasis vulgaris and subacute eczema pharmacological effect: interleukin-8 has chemotaxis on neutrophils According to the literature, the concentration of IL-8 in the skin of psoriasis lesions is higher than the normal level, which may be one of the factors for the early formation of psoriasis lesions The results of animal experiments suggested that the mechanism of action of the drug might be to reduce the aggregation of neutrophils by neutralizing IL-8 in local tissues, so as to reduce the reaction of skin inflammation Monoclonal antibodies can effectively neutralize excessive IL-8 in psoriatic lesions, thus preventing the infiltration of neutrophils into the skin, inhibiting the abnormal proliferation of epidermal keratinocytes, eliminating inflammation, and achieving the purpose of treating psoriasis 3 Manufacturer of recombinant human tumor necrosis factor receptor antibody fusion protein for injection: Guoyao Zhunzi s20050058 (12.5mg / bottle) and Guoyao Zhunzi s2005059 (25mg / bottle) of Shanghai CITIC Guojian Pharmaceutical Co., Ltd., approved on January 27, 2015 Indications: 1 Moderate and severe active rheumatoid arthritis; 2 Moderate to severe plaque psoriasis in adults aged 18 and over; 3 Active ankylosing spondylitis Pharmacological action: it is known that tumor necrosis factor (TNF-a) is a major inflammatory mediator in the pathological process of rheumatoid arthritis, psoriasis, ankylosing spondylitis and so on The inflammatory reaction involved in regulation can lead to pathological changes of joints The mechanism of action of the drug is to competitively bind to TNF-a in blood, block its binding to TNF receptor on cell surface and reduce its activity 4 Iodine [131I] tumor cell nuclear human mouse chimeric monoclonal antibody injection (aestheticism) manufacturer: Shanghai meien Biotechnology Co., Ltd gyzz s20060061, approved on August 31, 2006 Indications: it is suitable for radioimmunotherapy of advanced lung cancer which can not be controlled or relapsed by radiotherapy and chemotherapy Pharmacological effect: the drug is a 131I labeled human mouse chimeric monoclonal antibody for radioimmunotherapy of solid tumors The monoclonal antibody targets the nucleus of denatured and necrotic cells in the tumor necrosis area, transports its loaded radioactive 131I to the necrotic site of solid tumors, and produces killing effect on solid tumor tissue cells through its local radioactivity 5 Iodine [131I] metuximab injection (ricardine) manufacturer: Chengdu Huashen Biotechnology Co., Ltd Guoyao Zhunzi s2006064, approved on May 18, 2011 Indications: primary liver cancer that cannot be resected or recurred after operation, and advanced liver cancer patients that are not suitable for transcatheter arterial chemoembolization (TACE) or invalid or recurred after TACE treatment Pharmacological action: the drug is a new type of monoclonal antibody labeled with iodine [131I] for guiding radiotherapy of liver cancer Mitoximab-hab18f (ab ') 2 can bind with HAb18G antigen distributed in the membrane protein of hepatoma cells, and transport its loaded radioiodine [131I] to the tumor site, thus having antitumor effect 6 Manufacturer of nitzumab injection (taixinsheng): Baitai bio Pharmaceutical Co., Ltd gyzz s20080001, approved on December 25, 2012 Indications: it is suitable for the treatment of stage III / IV NPC with positive expression of epidermal growth factor receptor (EGFR) in combination with radiotherapy Pharmacological action: EGFR is a transmembrane glycoprotein with a molecular weight of 170kd, and its intracellular region has