Domestic PD - (L) 1 McAb R & D panorama Hengrui and Xinda encounter obstacles in the competition of taking the lead in listing

Source: minenet on March 27, 2018-04-09, the news that "xindimab was dissuaded" came out of the circle of friends, causing a sudden uproar On February 14 this year, Hengrui pharmaceutical announced that after negotiation with Incyte, the two sides signed an agreement to terminate the cooperation in the development of PD-1 monoclonal antibody shr-1210 The research and development of PD - (L) 1 monoclonal antibody by the two top domestic R & D pharmaceutical companies is not a smooth road, and the competition for the first listing of domestic PD - (L) 1 monoclonal antibody is still continuing With a huge market of 35 billion yuan, many enterprises have set up the field of tumor immunotherapy, and PD-1 / PD-L1 inhibitors have attracted the attention of drug developers since they came into being The global market share of PD-1 / PD-L1 inhibitors has exceeded 10 billion US dollars in 2017, and will grow at a compound annual growth rate of 23.4% by 2025, with a peak value expected to reach 35 billion US dollars The huge market has triggered fierce competition among large and small enterprises at home and abroad At present, five PD - (L) 1 monoclonal antibodies have been listed in the world, and they are in the leading position of Bristol Myers Squibb MSD is in pursuit of them Pharmaceutical giants Roche, Merck and AstraZeneca have entered into a fight one after another The gap between Bristol Myers Squibb and MSD's two heavyweight PD-1 McAbs is narrowing It is expected that MSD will achieve anti super in 2018 Bristol Myers Squibb opdivo submitted an application for listing in China on November 2, 2017 It is expected to be approved in the first half of this year Facing the huge anti-tumor market in China, it will further take the lead Keysruda submitted the application for listing in China on February 11, 2018, which is likely to become the second domestic listed PD - (L) 1 monoclonal antibody It is expected that 2018q3 will be approved Although domestic enterprises are slightly backward, they are also in the process of layout Up to now, more than 10 enterprises have carried out clinical trials, among which Junshi biology, Xinda biology, Hengrui medicine and Baiji Shenzhou are in the first echelon of research and development, with fierce competition Wildly beating gongs and drums, 23 domestic PD- (L) 1 mAbs, and the first emerging bubble in Table 1: the current research and development status of PD- (L) 1 mAb in domestic enterprises (source: rice net finishing, main statistics of domestic clinical trials) There are 23 domestic PD- (L) 1 monoclonal antibodies being vigorously promoted Among them, Jun Shi, XinDa, Heng Rui medicine and Baiji Shenzhou are the best ones At present, Junshi biology is relatively ahead of schedule On March 9, 2018, Junshi biology announced that js001's new drug listing application was officially accepted by CDE, and the indication is melanoma Js001 is the first PD-1 monoclonal antibody approved by CFDA clinical trial in domestic enterprises At present, js001 is carrying out more than 10 phase I-III clinical trials of indications such as melanoma, NPC, gastric cancer, lung cancer, esophageal cancer, urothelial cancer with a number of clinical centers in China The listing application of Cinda bio's Xindi mAb injection (PD-1 mAb) was accepted by CDE on December 13, 2017 The indication is Hodgkin's lymphoma At present, the listing application has been withdrawn Hengrui medicine and Baiji Shenzhou's PD-1 monoclonal antibody products are in the phase III test stage, and the indications are non-small cell lung cancer, esophageal cancer and liver cell cancer A large number of capital flows into PD- (L) 1 mAb, and the number of enterprises that can win from it is a minority, and the bubble has gradually formed Halo and pressure, the research and development of Hengrui and Xinda PD-1 has been hindered by Hengrui shr-1210, and the side effect of hemangioma has become the biggest obstacle to Hengrui's PD-1 monoclonal antibody shr-1210 It is the first PD - (L) 1 monoclonal antibody to enter the phase III clinical trial in China, and it is covered with multiple halos In May 2015, Jiangsu Hengrui sold its PD-1 antibody shr-1210 overseas (outside mainland China, Hong Kong, Macao and Taiwan) rights and interests to Incyte, a US pharmaceutical company, with a total down payment of US $25 million plus a mileage of US $770 million, which became a hit story On February 14 this year, Hengrui pharmaceutical announced that after negotiation with Incyte, the two sides signed an agreement to terminate the cooperation in the development of PD-1 monoclonal antibody shr-1210 The cooperation between the two famous pharmaceutical companies ended temporarily It is worth mentioning that Incyte introduced another PD-1 monoclonal antibody mga012 from macrogenesis in October last year for US $900 million for global development and Commerce of all indications Right, the move is intriguing Since the second half of 2017, it has been reported that "many patients who took part in the clinical trial of Hengrui PD-1 had hemangioma symptoms, and some of them have withdrawn from the trial." In the 2017 ASCO (American Society of Clinical Oncology), an article titled "phase I study of the antipd-1 antipodal shr-1210 in patients with advanced solid tumors" published the adverse reactions of 58 patients, 79.3% of the subjects had the symptoms of reactive capillary hemangioma With extensive side effects and withdrawal of partners, Hengrui pharmaceutical did not directly publish positive clinical trial results to respond to these adverse news, and all questions need time to wait for the final results Figure 1: side effect picture of hemangioma of a subject (source: well-known analyst in the industry suspected Xi Weibo) Xinda ibi308 was dissuaded!? in fact, Xinda biology voluntarily withdrew the listing application (cxss1700038) of Xindi mAb injection (ibi308) submitted by Xinda biology on December 13, 2017, which was accepted by CDE This is the first domestic application for listing of PD-1 monoclonal antibody, and the second application for listing in China after Bristol Myers Squibb opdivo At that time, the news that Xinda submitted the application for listing of PD-1 McAb was also a sensation, but it also attracted many questions One of the query points is that xindimab injection is "fast" from the clinical trial stage to the listing application stage According to medchina drug review database 2.0 on the intranet, since Xinda biology submitted the clinical application of xindimab on January 25, 2016, the product obtained the clinical approval on August 17, 2016, with the project name of ibi308, December 13, 2017, xindimab injection The application for listing is accepted by CDE From the initial submission of clinical trial application to the submission of listing application, it took 1 year, 11 months and 9 days, which was very fast The indication of xindimab for labor report is Hodgkin's lymphoma, and the corresponding clinical trial registration number is ctr20170281 The first public date of the indication is April 17, 2017 The registration information shows that the number of people in the group is 90 The subjects are injected intravenously every three weeks, and the maximum treatment time is 24 months 90 subjects, enrollment, physical examination, preparation After 6 months of observation, statistics and report, the indication was reported in the 7th month, and the rapid development of sindimab also made it suffer a lot of doubts (among them, "Unblinding ahead of time" was the most) This initiative withdrawal is a decision made by Xinda and CDE after too many rounds of communication It will be applied after the materials are supplemented It is a normal procedure, but the specific time required is hard to estimate, and the final result makes us wait patiently Figure 2: conclusion of search results of xindimab injection in Med China drug review database 2.0 on minenet since the drug review reform in 2015, many policies encouraging new drug research and development have been implemented, and many capitals have also poured into hot fields such as Pd - (L) 1 mAb and car-t therapy At present, nearly 20 enterprises in China have arranged the field of PD - (L) 1 monoclonal antibody, and carried out clinical trials in different tumor species The road of R & D is long and obstructed Hengrui and Xinda, who are in the front row, have encountered some obstacles to some extent, while the two heavyweight PD-1 McAbs of Bristol Myers Squibb and MSD are just like two mountains in front of domestic enterprises It remains to be seen who will become the first domestic enterprise to be approved for listing of PD - (L) 1 monoclonal antibody.