[dry goods] overview of independent research and development of small molecule anti-tumor drugs in China (Part I)

Cancer incidence rate and mortality rate in China has been increasing year by year It has become the main cause of death since 2010, and has become a major public health problem in China A considerable part of this increasing pressure can be attributed to population growth and aging, as well as changes in social demography In 2016, Ca-A cancer journal for clinicians, with an impact factor of 144.8, published an article of cancer statistics in China, 2015 published by Chinese scholars, namely 2015 China Cancer statistical report The authors analyzed population-based cancer registries (2000-2011) in 72 regions representing 6.5% of the population to estimate the number of new cancer cases and deaths in 2015 The results show that 4.292 million new cancer cases and 2.814 million deaths are expected in 2015 In July 2017, China Securities Journal published a piece entitled "a major breakthrough in the anti-tumor drug market", citing the data of Caihui financial big data terminal, saying that in 2016, the global drug spending for cancer treatment was $110 billion, far higher than that for other diseases Large patient population, huge market space and far unmet clinical treatment demand, more and more pharmaceutical enterprises are absorbed into the research and development of anti-tumor drugs, among which there are many domestic enterprises From September 8 to 10, the 2017 China Pharmaceutical Summit Forum and the top 100 list of R & D strength of pharmaceutical enterprises jointly sponsored by yaozhi.com and China Pharmacy magazine launched in Chongqing The conference will solemnly release the 2017 ranking of R & D strength of pharmaceuticals (including the "general list", "chemical list", "Chinese medicine list", "biological medicine list" and "brand list"), which anti swelling The leading enterprises of oncology drugs will be shortlisted in the 2017 ranking of drug R & D strength by virtue of their solid R & D strength? Welcome to the venue Based on the registration and acceptance data of smart drugs, the registration and information publicity platform of clinical trials on CDE website, combined with sufficient literature search, this paper introduces the following information of small molecule anti-tumor drugs independently or cooperatively researched and developed by domestic enterprises under various indications and in the publicity stage of clinical trials: * pharmacological characteristics, especially the target *The application acceptance and approval time can reflect the policy support * clinical trial information, mainly including: the name of the trial specialty reflecting the type and main purpose of the clinical trial, the trial publicity time, the trial status, the trial plan / the actual number of participants and the enrollment time of the first subject The literature includes: periodical literature, dissertations, media reports and information independently disclosed by the company 1 respiratory system tumors, according to the 2015 China cancer statistics report, in 2015, 733 thousand and 300 new lung cancer patients and 610 thousand and 200 deaths were predicted in China Incidence rate and mortality rate rank first 1.1 bpi-15086 bpi-15086 is the third generation of EGFR inhibitor small molecule targeted anti-tumor drug independently developed by Beida Pharmaceutical Co., Ltd However, according to the published clinical trial information, the drug can also overcome the drug resistance caused by T790M mutation The clinical application of its APIs and tablets was accepted in November 2015 (category 1.1), and was approved in August 2016 after special review *Advanced NSCLC - highest status: phase I, subject recruitment has not been initiated On September 20, 2016, the drug clinical trial registration and information publicity platform announced "phase I clinical study (Registration No.: ctr20160704) of bpi-15086 in patients with T790M mutant advanced non-small cell lung cancer (NSCLC) who have progressed after the previous EGFR-TKIs treatment" The trial has not yet started the recruitment of subjects, and plans to enroll 80 people 1.2 bpi-9016m bpi-9016m is a small molecule Axl inhibitor targeting anti-tumor drug independently developed by Beida Pharmaceutical Co., Ltd its action target also includes hgfr At present, there is little information related to the drug Its clinical application for APIs and capsules was accepted by CDE in April 2016 (category 1.1), and was approved for clinical application in January 2017 after special review *Advanced non-small cell lung cancer with abnormal c-met - highest status: phase I, subject recruitment has not been initiated On October 9, 2016, the drug clinical trial registration and information publicity platform announced a phase IB clinical study on the safety, tolerance, efficacy and pharmacokinetics of bpi-9016m in advanced NSCLC patients with abnormal c-met (Registration No.: ctr20160757) The trial has not yet started the recruitment of subjects, and plans to enroll 50 people 1.3 Hemay 020 Hemay020 is a small molecule targeting anti-tumor drug of EGFR irreversible inhibitors jointly developed by China Pharmaceutical and Health Industry Co., Ltd and Tianjin Hemei Biotechnology Co., Ltd in July 2012, Hainan Santong Sanyo Pharmaceutical Co., Ltd., a wholly-owned subsidiary of China Pharmaceutical and Health Industry Co., Ltd., submitted the clinical application of API and capsule according to category 1.1, and then passed the special The review was approved in July 2014 *Non small cell lung cancer - highest status: phase I, the platform for registration and information publicity of clinical trials of Chinese drugs recruited by subjects published a "small molecule EGFR tyrosine kinase irreversible inhibitor hemay 020 capsule for phase I clinical trials of advanced solid tumors" on June 25, 2015, with the mark of ctr20150294 The trial includes two parts: dose increasing study and extended study The extended study takes patients with advanced EGFR wild-type non-small cell lung cancer (or undetermined genotype) as the study object, which is still in the recruitment stage of subjects The first subject was enrolled on July 3, 2015, totally 55 people were included in the group 1.4 plb1003 plb1003 is an antineoplastic drug declared by Beijing puruno Biotechnology Co., Ltd according to category 1.1 There is no information related to its action target for the moment However, according to the inclusion criteria provided by its published clinical trials, the drug may act on ALK receptor tyrosine kinase The new drug clinical application of plb1003 API and capsule was accepted by CDE in December 2015, and was approved by special review in August 2016 for clinical, * ALK positive advanced non-small cell lung cancer phase I, highest status: subject recruitment stage In February 2017, the drug clinical trial registration and information publicity platform publicized a "single center, open, single arm, dose increasing phase I study (ctr20170023) on plb1003 capsule for patients with ALK positive advanced non-small cell lung cancer (NSCLC)" The trial has started the recruitment of subjects and plans to enroll 30 people, but the time for the first subject to enroll has not been disclosed 。 1.5 sph1188-11 sph1188-11 is a small molecule targeting anti-tumor drug of EGFR inhibitors developed by Shanghai Pharmaceutical Group Co., Ltd the clinical application of its APIs and tablets of class 1.1 new drugs was accepted by CDE in April 2016, and was approved for clinical application in December 2016 after special review *Locally advanced or metastatic NSCLC - highest status: phase I, subject recruitment phase On June 9, 2017, the drug clinical trial registration and information publicity platform announced a "preliminary exploration research plan on the safety, tolerance, pharmacokinetics and efficacy of phase I, open, sph1188-11 in the treatment of locally advanced or metastatic non-small cell lung cancer (Registration No.: ctr20170556)" The trial has started the recruitment of subjects, and the first subject was enrolled on July 21, 2017, with a total of 18-36 people are planned to join the group 1.6 beretinib is a class 1.1 new drug declared by Beijing puruno Biotechnology Co., Ltd in April 2014 After special review, beretinib was approved in June 2015 for clinical use, and its enteric coated capsule is planned to be used as medicine There is less relevant information in the professional database, and it is reported that the target of beretini is c-met *Non-small cell lung cancer with abnormal c-met - highest status: phase I, subject recruitment phase On April 27, 2016, the platform for registration and information publicity of drug clinical trials published a phase I, open, multicenter, dose increasing and extended study (Registration No.: ctr20160228) to investigate the tolerance and pharmacokinetics of beretinib in NSCLC patients with abnormal c-Met, which is still in the recruitment stage of subjects The first subject was enrolled on April 25, 2016, and it is planned to 30 people 1.7 furetinib succinate is the second generation of ALK inhibitor anti-tumor drug developed by Chongqing fuchuang Pharmaceutical Research Co., Ltd in March 2015, with the support of new drug creation project, the clinical application of API and capsule (class 1.1) was submitted, and the clinical trial was approved on October 20, 2015 after special review *ALK positive non-small cell lung cancer - highest status: phase II, subject recruitment has not been initiated On July 6, 2016, the drug clinical trial registration and information publicity platform publicized a "phase I study on dose exploration of furetinib succinate in patients with ALK positive advanced malignant solid tumor and phase II study in patients with ALK positive non-small cell lung cancer (Registration No.: ctr20160339)" The trial has not yet started the recruitment of subjects, and a total of 196 people are planned to enter the group 1.8 efetinib mesylate (ast2818) is a class 1.1 new drug developed by Shanghai Elis Pharmaceutical Technology Co., Ltd., which is specially designed for egfrt790m resistant non-small cell lung cancer In the preclinical study, efetinib mesylate showed good antitumor activity against T790M resistant tumors; the drug was widely distributed in animals and could pass through the blood-brain barrier No adverse reactions such as cardiotoxicity, ocular toxicity and hyperglycemia were found in the preclinical study of the drug, which showed good safety The clinical application for new drugs of efetinib mesylate APIs and tablets was accepted by CDE in January 2016, and was approved for clinical application in September 2016 after special review *Advanced non-small cell lung cancer - highest status, phase I / II, subject recruitment phase drug clinical trial registration and information publicity platform published a "multicenter, single arm phase I / II clinical trial (Registration No.: ctr20170447) to evaluate the efficacy and safety of efetinib mesylate in advanced NSCLC patients after 1 / 2 generation EGFR-TKI treatment" on June 28, 2017 The trial has started the recruitment of subjects The first subjects were enrolled on June 2, 2017, with a total of 81 planned 1.9 avetinib maleate (ac0010) is the third generation EGFR tyrosine kinase inhibitor small molecule targeted anti-tumor drug developed by Hangzhou Essen Pharmaceutical Research Co., Ltd with the support of new drug development project It can overcome the drug resistance caused by T790M mutation Its structural formula is shown in the following figure The clinical application of ivetinib maleate APIs and capsules submitted by Eisen pharmaceutical under the special support of new drug creation was accepted by CDE in August 2013, and then approved by special review in September 2014; then the supplementary application submitted under the special support of new drug creation was accepted by CDE in June 2016, and approved in September *Advanced NSCLC - highest status: phase II, subject recruitment phase A single arm, multicenter, phase II clinical trial (Registration No.: ctr20161010101018) on efficacy and safety of ivertinib maleate capsule in the treatment of egfrt790m mutation positive advanced NSCLC patients was publicized by the drug clinical trial registration and information publicity platform on December 30, 2016 The trial is still in the recruitment stage, and the first subject was enrolled on May 18, 2017, with a total plan of enrollment Group 222 An article published in annals of oncology in 2016 disclosed the preliminary results of the phase I clinical trial (nct02274337) of ivetinib maleate conducted in the same period abroad In this study, patients with non-small cell lung cancer were treated with ivertinib after the first generation of TKI resistance