[depth] PD-1: the top three domestic companies use the first mover advantage to block the latecomers

The domestic market of PD-1 / PD-L1 monoclonal antibody has entered the stage of drug commercialization from the stage of drug research and development On June 15, 2018, opdivo (BMS) was approved to be listed by nmpa, becoming the first approved PD-1 monoclonal antibody in China In a short period of one year, nmpa approved the listing of five kinds of PD-1 monoclonal antibodies, including two imported ones (opdivo, BMS, keytruda, MSD), three domestic ones (treprizumab (tuoyi, Junshi Biology), cindili monoclonal antibody (Dabusu, Cinda Biology), and carrizumab (Alito, Hengrui medicine) ) So far, three other PD-1 / PD-L1 mAbs (tirelizumab (Baiji Shenzhou), imfinzi (AstraZeneca), tecentriq (Roche)) have also submitted their listing applications to nmpa, among which the approval of Baiji Shenzhou PD-1 is imminent There are 6 monoclonal antibodies of PD-1 / PD-L1 in the European and American markets, including 3 monoclonal antibodies of PD-1 and 3 monoclonal antibodies of PD-L1 Among them, keytruda and opdivo, BMS, which were first listed in 2014, have become the top 10 best-selling drugs in the world In 2018, the total sales of PD-1 / PD-L1 McAbs in the global market has exceeded 15 billion US dollars The commercialization process of PD-1 / PD-L1 McAb in European and American market for 5 years is of great significance to the domestic market of PD-1 / PD-L1 McAb At present, there are as many as 20 PD-1 / PD-L1 McAbs on the market and in the middle and later stage of clinical trials in China, including 13 PD-1 McAbs and 7 PD-L1 McAbs The PD-1 mAbs of BMS, mosadong, Junshi biology, Xinda biology and Hengrui medicine have been approved for listing since June 2018 Meanwhile, the PD-1 mAbs of Baiji Shenzhou and the PD-L1 mAbs of Roche and AstraZeneca are applying for listing, which is expected to be approved in the second half of this year Referring to the commercialization process of PD-1 / PD-L1 monoclonal antibody in overseas market, the approximate rate is that four foreign enterprises, BMS, MSD, Roche and AstraZeneca, together with four local enterprises, Junshi biology, Xinda biology, Hengrui medicine and Baiji Shenzhou, have become the head enterprises in domestic PD-1 / PD-L1 monoclonal antibody market, forming a "4 + 4" pattern The head enterprises will use the first mover advantage to share most of the cake in the domestic market of PD-1 / PD-L1 McAb in the future, and the latter enterprises can only conduct differentiated competition in strategy According to the National Cancer Center, the incidence rate of the top five cancers in the country are lung cancer, gastric cancer, colorectal cancer, liver cancer and breast cancer Lung cancer is the most common cancer incidence rate and mortality rate in China, accounting for nearly 20% of the total number of cancer cases According to the World Health Organization (who) pathological classification, lung cancer can be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) Among them, SCLC accounts for about 10-15% of lung cancer, NSCLC accounts for about 85% of lung cancer, which can be subdivided into adenocarcinoma (40% - 50%), squamous carcinoma (30-40%) and large cell carcinoma (< 10%) According to the main clinical progress of the head enterprises of PD-1 / PD-L1 McAb in China, the layout of combined drugs has occupied more than 50%, which has become the top priority of the research and development of major pharmaceutical enterprises Because the clinical efficacy of the combination of PD-1 / PD-L1 McAb is very good, on the one hand, it can increase the success rate of clinical trials, on the other hand, it can use the conditional approval and priority review policy of nmpa to speed up the approval speed and seize the market (for example, Hengrui PD-1 McAb applies for the treatment of HCC) However, for the enterprises that are lagging behind in the research and development of PD-1 / PD-L1 monoclonal antibody, it will be a good opportunity to overtake on the curve if the combination of small molecule drugs and monoclonal antibody drugs can obtain conditional application for listing on the unapproved indications with good efficacy Five kinds of PD-1 monoclonal antibodies approved for marketing in China have published the price and drug donation assistance plan The price of nevulizumab, pabolizumab and carrizumab is relatively high, with an annual cost of more than 500000 yuan The price of treprizumab and cindilimab is relatively low, with an annual cost of 187000 yuan and 282000 yuan, respectively If we can get drug donation assistance, the annual cost of treprizumab and carrizumab is relatively low, and the annual cost can be reduced to about 100000 yuan The price of PD-1 monoclonal antibody made in China is lower than that of imported products If there is no significant difference in efficacy, the accessibility of PD-1 monoclonal antibody made in China is higher Specifically, the price of trepril mAb of Junshi biology is relatively high, with the lowest price; the price of sindeli mAb of Cinda biology is in the middle; the price of carrelizumab of Hengrui medicine is relatively high, but the price can be reduced to a lower level after drug donation assistance Local companies mainly adopt the low-cost sales strategy to make up for the lack of commercialization ability, while the drug donation assistance plan also provides a flexible pricing for PD-1 monoclonal antibody Hengrui medicine has left more flexibility to its own PD-1 monoclonal antibody through the drug donation assistance plan, which can not only ensure the high price to maintain profits, but also maintain the market competitiveness through drug donation assistance, and also maintain the market competitiveness for the future The price reduction of medical insurance has a certain ability to resist pressure.