Review of the development of bio medicine in China in 2019

By Qin Lunan 2019 is a year of vigorous development in the field of Biopharmaceutics in China, as well as a year of continuous improvement of laws, regulations and regulatory system ·In terms of biopharmaceutical products, vaccine companies accelerated the layout of multi linked multi valent vaccines and new vaccines; the first domestic bio similar drug rituximab and the first domestic adalimumab were approved for listing; several domestic third-generation insulin products were applied for listing; nine cell therapy products and four gene therapy products were accepted by CDE for clinical trials ·From the perspective of investment and financing, 7 bio pharmaceutical innovation enterprises went to Hong Kong for IPO, including 6 in the field of antibody drugs and 1 in vaccine research and development ·From the perspective of regulatory policies, the vaccine management law of the people's Republic of China was promulgated, and a number of policies were issued to accelerate drug review and approval and establish an information-based drug traceability system Two products are on the market, and domestic product innovation is increasing From January to December 31, 2019, China's CDE accepted 6 domestic vaccines, 3 imported vaccine clinical trials and 6 domestic vaccine marketing applications, and approved one domestic vaccine and one imported vaccine From the perspective of product type, the domestic vaccines accepted by clinical trial application and marketing application are mostly new vaccines and multi linked multi valent vaccines, such as Tetravalent Recombinant norovirus vaccine and 13 valent pneumococcal polysaccharide combined vaccine of zhifeilongcoma It can be seen that domestic vaccine enterprises continue to increase innovation and research in recent two years The imported vaccines brii-179, obi-822 and vgx-3100 that have been accepted for clinical trials are therapeutic vaccines, which shows that foreign countries are in a leading position in the field of therapeutic vaccines Data source: flint creation The domestic vaccine approved for marketing is the tetravalent influenza vaccine of Jiangsu jindick, which is the second approved product after the tetravalent influenza vaccine of Hualan biology The imported vaccine approved for marketing is GSK recombinant herpes zoster vaccine, which is composed of glycoprotein E recombinant protein of varicella zoster virus and new adjuvant AS01B Clinical results showed that the vaccine showed more than 90% of the efficacy of herpes zoster prevention in all age groups Data source: flint creation More than 200 products accept clinical applications, and several heavy-duty products are on the market From January to December 31, 2019, CDE accepted a total of 100 applications for clinical trials of domestic antibody drugs (including different indications), 119 applications for clinical trials of imported antibody drugs (including different indications), and 12 applications for listing of domestic antibody drugs (including different indications) There were 4 approved domestic antibody drugs and 5 imported antibody drugs From the perspective of antibody drugs accepted for clinical trials, Hengrui medicine, Xinda biology, and baiaotai have made outstanding achievements For example, Hengrui medicine has invested more than 615 million yuan in the research and development of carrelizumab In 2019 alone, seven new clinical trials for indications have been accepted for this product; foreign giants Roche, Novartis and MSD have received a number of products, for example For example, Roche's PD-L1 antibody atilizumab has 9 applications for clinical trials of indications accepted, the global sales of the product last year increased by 59% year-on-year; mesardon's heavyweight product pabolizumab has 10 applications for clinical trials of indications accepted, the global sales of the product in 2018 reached US $7.171 billion, a number of heavyweight products accelerated, indicating that overseas giants are optimistic The market prospect of antibody drugs in China From the perspective of the domestic antibody drugs accepted by the listing application, the national first-class new drug of Rongchang biology, taitasipu, was approved for the treatment of systemic lupus erythematosus The clinical data showed that its treatment effect was better than that of beryluzumab, GSK, and the treatment cost was lower in the future Fuhong Hanlin and Junshi biology are the fourth and fifth domestic enterprises that have submitted the listing application of adamumumab, respectively Fuhong Hanlin has invested nearly 200 million yuan in research and development of this product In terms of the approved domestic antibody drugs, rituximab of Fuhong Hanlin is the first domestic bio similar drug approved for the treatment of lymphoma; PD-1 monoclonal antibody of Hengrui medicine is approved for the treatment of relapsed / refractory Hodgkin's lymphoma; adalimumab of baiaotai is the first biological drug approved for the treatment of ankylosing spondylitis; Baiji Shenzhou In Hodgkin's lymphoma, the cure rate of drugs O and K was only 20%, while that of tirelizumab was as high as 60% From the perspective of the approved imported antibody drugs, Johnson's daretosuzumab is the first CD38 mAb in China and approved for the treatment of multiple myeloma; Amgen's desumab, as a drug in urgent need of overseas listing, has been approved for the treatment of giant cell tumor of bone; GSK's berryuzumab is the first new drug for the treatment of lupus erythematosus in 60 years; yushibi's peserizumab has been approved for the treatment As a kind of medicine which needs to be sold abroad urgently, elilai's iqizumab has been approved for the treatment of plaque psoriasis Multiple diabetes treatment products are accepted by CDE From January to December 31, 2019, CDE accepted clinical trial applications of 13 domestic recombinant proteins, 6 imported recombinant proteins, and 8 domestic recombinant protein listing applications There were 3 domestic recombinant proteins and 4 imported recombinant proteins approved for listing From the perspective of recombinant protein accepted by clinical trial application, there are many recombinant insulin products in domestic enterprises, among which degu insulin of Zhengda Tianqing, aspart insulin of UL and Dieter insulin of Cr ONDE are the third generation of recombinant insulin A number of heavy-duty products of foreign enterprises have been accepted, including Novartis' diabetes drug oral lilalutide and Ansun's breakthrough antiviral drug das181 Data source: flint creation From the perspective of recombinant proteins accepted by listing applications, there are many innovative products, including insulin aspartame from Haizheng pharmaceutical, Tonghua Dongbao, and insulin glargine from Boao biology; Newland green, the first new drug of Zesheng technology used to treat chronic heart failure; the first domestic recombinant human coagulation factor VIII independently developed by Shenzhou cell in ten years From the perspective of the approved recombinant protein, the generic recombinant trypatide of xinlitai is the second domestic product with low price after marketing, which is expected to significantly reduce the cost of treatment for osteoporosis patients The digumendon double insulin injection of Novo Nordisk is the first domestic soluble double insulin preparation, which can not only play the long-term, stable and peak free hypoglycemic effect of degu insulin Potential, but also to play the role of insulin asparagus rapid hypoglycemic, taking into account basic blood sugar and postprandial blood sugar control, to achieve complementary advantages Table 4 Domestic Recombinant Protein approved for marketing in 2019 Data source: flint creation Table 5 imported recombinant protein approved for marketing in 2019 Data source: flint creation A number of clinical applications for heavy-duty products have been approved, and no products have been put on the market temporarily From January to December 31, 2019, CDE accepted clinical trial applications for 13 domestic cell and gene therapy products (5 immunocell therapy products, 4 stem cell therapy products, 4 gene therapy products), 2 imported cell therapy products (1 immunocell therapy product, 1 stem cell therapy product), no product application or approval for marketing From the perspective of cell therapy products accepted by clinical trial application, the immunotherapy products of domestic enterprises are all car-t, and the targets are all CD19; there are three mesenchymal stem cell products and one lung basic epithelial cell product (regend001) in the stem cell therapy products of domestic enterprises One immunocell therapy product of a foreign enterprise is ctl019 produced by Novartis, which was approved to market in the United States in 2017, and is the first car-t approved to market in the world In 2019, two clinical trials of indications were accepted by CDE; the ischemic tolerance human bone marrow mesenchymal stem cells of stemeca, a foreign enterprise, can be used for the treatment of ischemic stroke, and the phase I / II clinical trials carried out in the United States Positive results have been achieved From the perspective of gene therapy products accepted by clinical trial application, all four products are oncolytic viruses Table 6 clinical trial application of domestic cell and gene therapy products accepted by CDE in 2019 Data source: flint creation （1） China's bio pharmaceutical enterprises are listed on the Hong Kong Stock Exchange Since 2018, the Hong Kong Stock Exchange has revised the listing rules to open a "green channel" for the listing of unprofitable biotechnology companies, which has triggered the upsurge of IPO of biotechnology companies in Hong Kong Stock Exchange in 2019 In 2019, there are 7 Chinese bio pharmaceutical enterprises IPO on the Hong Kong stock exchange, 6 of which are in the field of antibody drugs, and 1 is a vaccine R & D enterprise Table 7 bio pharmaceutical enterprises listed on the Hong Kong Stock Exchange in 2019 Data source: flint creation （2） Over 60% of antibody financing In 2019, a total of 7.551 billion yuan of financing was generated in the field of biological drugs, including 4.957 billion yuan for antibody drugs, 2.029 billion yuan for cell and gene therapy, 315 million yuan for recombinant protein and 250 million yuan for vaccines Figure 1 proportion of financing amount in various subdivisions of bio medicine in 2019 Data source: flint creation The largest amount of financing was obtained by zaiding pharmaceutical, an antibody drug R & D and production enterprise, with a strategic financing of 1.4 billion yuan, followed by Genxi biology, a cell therapy enterprise, with a round B financing of 595 million yuan Table 8 financing record of over 100 million yuan of bio pharmaceutical enterprises in 2019 Data source: flint creation In 2019, the policies in the field of Biopharmaceutics are mainly in three aspects: establishing an information regulatory system, meeting the R & D needs of R & D enterprises, and accelerating drug review and approval The most important policy is the release of the vaccine management law of the people's Republic of China Table 9 review of relevant key policies in the field of biological drugs in 2019