Hengrui, Junshi, Xinda and Baiji are competing for supremacy, and the first echelon of PD-1 market is competing for listing! The war is on!

Source: e drug manager 2018-06-05 Hengrui PD-1 is the fifth McAb applying for listing in China BMS, MSD, Junshi and Xinda have submitted listing applications before it The first echelon of domestic PD-1 listing has been formed On April 23, 2018, the listing application (cxss1800009) of camrelizumab (shr-1210) for Hengrui PD-1 monoclonal antibody injection was accepted by CDE, and it is planned to be included in the 28th batch of priority review, adding another fire to the development competition of PD-1 monoclonal antibody in the burning oil At present, Hengrui's PD-1 monoclonal antibody is the fifth one to be listed in China Prior to this, opdivo of BMS overseas, keytruda of MSD, and PD-1 mAbs of domestic Junshi and Xinda have all submitted listing applications Among them, Opdivo of BMS took the lead in submitting the listing application on November 1, 2017, becoming the first PD-1/PD-L1 target drug to be listed in China The first domestic application was submitted by Cinda bio on December 13, 2017 (later withdrawn and resubmitted on April 19, 2018) From a global perspective, BMS, MSD, Roche and AstraZeneca are the first echelon; from a domestic perspective, they are also the top four players, namely Hengrui medicine, Xinda biology, Junshi biology and Baiji Shenzhou In addition to the fact that Baiji Shenzhou may be slow to be listed due to the international multicenter clinical trials, three other companies have reported their applications for listing It is worth noting that PD-1 / PD-L1 drug research and development is hot in China, with 30 PD-1 / PD-L1 drugs under research, and more than 60 clinical trials about to be carried out or in progress publicized by CFDA at present PD-1 medicine is a collective appearance of China's innovative pharmaceutical enterprises, which will also test the overall strength of enterprises including R & D capacity, production capacity and academic promotion capacity 1 There are 5 monoclonal antibodies of PD-1 / PD-L1 in the world with increasingly fierce competition, and the total sales volume exceeds 8 billion US dollars (see Table 1) Among them, opvido, jointly developed by keytruda, BMS and Ono pharmaceutical of MSD, takes the lead in sales due to many indications approved earlier The opdivo of BMS is the first FDA approved PD-1 McAb in the world It was approved by PMDA in July 2014, FDA in December 2014 and EMA in 2016 Keysruda is the first PD-1 McAb approved by FDA It was approved by FDA in September 2014 and approved in the United States three months faster than opdivo It was approved in Europe and Japan in 2015 and 2016 respectively After that, Roche, AstraZeneca and Pfizer respectively launched their corresponding PD-L1 McAbs to compete in the PD-1 market From the perspective of the application progress of PD-1 monoclonal antibody of domestic pharmaceutical enterprises, Xinda, Junshi and Hengrui belong to the first echelon, and Baiji Shenzhou has not yet reported production At present, more than 25 varieties have applied for the clinical application of PD-1 / PD-L1 McAb in China On February 8, 2018, CDE issued the basic requirements for data of application for listing of anti-PD-1 / PD-L1 McAb varieties, allowing the applicant to apply for listing of research results with orr as the main end point, which can be submitted on a rolling basis (see Table 2) After that, Cinda biology voluntarily withdrew the previous declaration and resubmitted the application on April 19, 2018, during which Junshi biology submitted the listing application on March 20 Baiji Shenzhou, also in phase III clinical stage, has not yet submitted an application for listing From the perspective of indications, at present, Hengrui has a more comprehensive coverage of indications, and the overall progress is faster Js001 of Junshi was declared as melanoma indication, and the indication of Cinda was Hodgkin's lymphoma According to the time of clinical trial and drug use, it is speculated that the rate of shr-1210 submitted by Hengrui will be declared as the classic indication of Hodgkin's lymphoma From the aspect of indication coverage of clinical trials, Hengrui has entered into phase III clinical indications for HCC, NSCLC and esophageal cancer Meanwhile, the indications for gastric cancer, NK / T-cell lymphoma and Hodgkin's lymphoma have reached phase II clinical, which is more advantageous than other two companies in the expansion of indications Referring to the competition between opdivo and keytruda in foreign countries, the expansion of indications is particularly important for the sales of PD-1 monoclonal antibodies Hengrui has certain advantages in this regard with its strong R & D strength and scale advantages (see Table 3) From the comparison of clinical data, the therapeutic effects of Hengrui, Junshi and Baiji Shenzhou are similar, and Hengrui has the side effects of microangioma In June 2017, Hengrui Medicine published the clinical data of PD-1 monoclonal antibody phase I on ASCO The orr of 29 cases of esophageal squamous cell carcinoma was 34.48%; that of 8 cases of gastric cancer was 37.50%; that of 3 cases of lung cancer was 1; that of 3 cases of NPC was 1; that of 3 cases of HCC was 1; that of 3 cases of colorectal cancer was 1; that of bladder cancer was 1 The total response rate was 31.0%, and the disease control rate was 46.5% Compared with PD-1 monoclonal antibody of Junshi and Baiji Shenzhou, the therapeutic effects of the three are similar (see Table 4) Shr-1210 of Hengrui has the side effects of hemangioma The incidence of hemangioma in domestic phase I trial is 79% and in overseas phase I trial is 61% However, most of them are mild level 1 side effects, which have little impact 2 Priority evaluation helps the three major domestic mAbs to be included in the priority evaluation, and the competition in PD-1 market is more intense CDE announced the list of drugs to be included in the 28th batch of priority review this time The PD-1 mAbs of Hengrui, Junshi and Xinda were included because of their obvious treatment advantages compared with the existing treatment methods Prior to this, the opdivo of BMS has been included in the priority review list The addition of Hengrui, Junshi and Xinda will speed up the time for domestic PD-1 monoclonal antibody to be launched in China The drugs of BMS and MSD have been listed overseas, so they are more secure in safety and effectiveness In contrast, domestic drugs have certain advantages in price and sales depending on the advantages of the company in China Several drugs, especially the declaration time is almost the same, the domestic market competition of PD-1 drugs will be more intense The number of class 1 new drugs submitted to NDA has increased to 4, and the innovative drug strategy is a step closer For Hengrui, the application and inclusion of shr-1210 in the priority review mean that its innovative drug strategy is another step forward At present, the company has 17 innovative drugs in the process of clinical development Many innovative drugs are in the phase III clinical trial or production application stage, including pyrrolidine, 19K, famitinib, shr-1210, etc., among which pyrrolidinib, 19K, rimazolen have applied for listing, pyrrolidinib has entered the priority review in 2017, and is expected to be approved for listing in 2018 When shr-1210 entered the market application, the number of class 1 new drugs submitted by Hengrui to NDA increased to 4, and 2 of them belonged to the priority review It is expected that a benign and sustainable development trend will be formed in the future, in which new drugs will be approved and listed every two to three years Prior to the listing of apatinib, the performance of Hengrui's anti-tumor drug sector has significantly improved Because of the wide indications, there is a huge market space for PD-1 monoclonal antibody in the future.