[exclusive] analysis of drugs included in the priority review: Zhengda Tianqing, Hengrui, Huahai, Bayer, Novartis

Highlights: 1 Trend of undertaking, 2015-2016 key year; 2 Approval rate of production report: new drug 25.78%, generic drug 26.84%, imported drug 65.82%; 3 Clinical approval rate: new drug 78.69%, generic drug 50%, imported drug 55.24%; 4 Class 1 new drug: clinical approval rate 92.31%; 23 production report preparations are worth waiting for, and Baiji Shenzhou, Hengrui and other heavy products are listed; 5.3 types of generic drugs: 5 kinds of batch production, 33 kinds of evaluation, Hengrui, Renfu, Zhengda Tianqing big competition; 6 Priority evaluation of the number of top three enterprises: new drug Zhengda Tianqing, Hengrui, hausen, generic drugs Huahai, dongyangguang, Qilu, imported drugs Bayer, Novartis, bringer Ingelheim, Pfizer 1 As of February 23, 2019, 791 drug acceptance numbers have been included in the priority review Among them, generic drugs accounted for the most, accounting for 39.70%, followed by new drugs, accounting for about one third Among the 791 applications for acceptance number, the time of undertaking is as follows, among which the drugs undertaken in the past three years are the most included in the priority review In addition, the number of new drugs included has increased in a straight line in the past eight years, surpassing import applications in 2018 It can be seen that driven by policies and innovation, more and more countries are entering the harvest period of new drug research However, the number of priority applications for generic drugs included in 2015-2016 was less than that of imports and new drugs, which had a certain relationship with the period when the generic drugs were in the transformation stage After the wind tunnel, the number of generic drugs increased greatly in 2017 and 2018, and the popularity returned again The following is a detailed analysis from three dimensions: declaration type of new drugs, generic drugs and imported drugs 2 Brief analysis of application types 2.1 new drugs 2.1.1 application and approval of new drugs included in the priority review mainly because of innovative drugs with obvious clinical value, major special projects, children's drugs, new drugs for rare diseases, new drugs with obvious treatment advantages, etc At present, there are 189 acceptance numbers of new drugs listed in the priority review The main applications are production application, with 128 numbers, accounting for 67.72% 33 acceptance numbers have been approved, with the approval rate of 25.78% Although the number of clinical application is less than that of labor application, the approval rate is higher, reaching 78.69% 2.1.2 in terms of the number of application acceptance numbers (including API) of the applicant enterprises, Zhengda Tianqing has the largest number of applications, up to 17, followed by Hengrui pharmaceutical and hausen pharmaceutical As the domestic enterprises with more new drug output, the number of drugs included in the priority review of 3 enterprises can also be seen to some extent the recognition of their innovation The following is a brief look at the specific declaration of 3 enterprises Zhengda Tianqing and Zhengda Tianqing No 12 in total (3 varieties, 5 APIs) were included in the priority review Five APIs were the first class of new chemical drugs, i.e arotinib hydrochloride (approved for production); four class 3.1 APIs, i.e fosapitam, diglucoside acetate, tenofovir dipivoxil fumarate (approved for production) and disodium gadolinate The three kinds of preparations were: arotinib hydrochloride capsule, fosartan bismeglumine for injection (under review and approval), and budesonide formoterol powder inhalation (capsule type) (clinical approval) Among them, the production of the 3-product specification of androtinib hydrochloride capsule has been approved according to the class 1 Application of chemical medicine, and the application of the 6-product specification according to the class 2.4 new drug of chemical medicine is currently under review and approval Hengrui medicine Hengrui medicine has a total of 12 acceptance numbers (4 varieties, 7 APIs) Its 7 APIs are: chemical medicine class 1 API new drugs: rimazolom toluenesulfonate, pyrrolidine maleate, chemical medicine class 3.1 API new drugs: paribonitol, fondaparinux, gadolinium butol, difluorane, and kapofungin acetate (approved for production) The four kinds of preparations are: rimazolom toluenesulfonate for injection, pyrrolidine maleate tablets (2 product specifications, approved for production), dexmedetomidine hydrochloride nasal spray (approved for clinical use), and carrizumab for injection, a new biological product It is worth noting that carrizumab for injection is a humanized anti-PD-1 monoclonal antibody, which can combine with human PD-1 receptor and block the PD-1 / PD-L1 pathway, restore the anti-tumor immunity of the body, thus forming the foundation of cancer immunotherapy At present, keytruda of mosadong company, opdivo of Bristol Myers Squibb Company, trepril mAb injection of Junshi biology and sindili mAb injection of Cinda biology have been listed in China Haosen pharmaceutical declaration No 8 (2 varieties, 4 APIs) of Haosen pharmaceutical Its 4 APIs are: chemical medicine 3.1 APIs: kafenjing sodium, bortezomib (approved for production), chemical medicine 1 APIs: flumatinib mesylate, polyethylene glycol loseptide The two kinds of preparation are the first class of new chemical drugs, flumatinib mesylate tablets and pegylated loseptide injection 2.1.3 in the registration and classification of new drugs, it can be seen that the number of new drugs in the first class (1.1) is the largest, accounting for 104, accounting for 55.02% Class 1 new drugs are very innovative, which represents the highest level of drug innovation in drug registration and classification in China Because of its difficulty in development and huge investment, it has the highest degree of attention Class 1 new drug (1) application for clinical application: the approval rate is 92.31% There are 39 class 1 new drug applications in Chongqing Qiuwen class 1 Traditional Chinese medicine and Beijing nuoling major special review, of which 36 (6 class 1 new drug applications) have been approved, and the approval rate is 92.31% Jnsw10032 and its tablets, a class 1 Traditional Chinese medicine declared for Chongqing Qiuwen biology, were included in the 27th batch of priority review on March 28, 2018, with the reason of "innovative medicine with clinical value"; it is worth mentioning that jnsw10032 is also the only application for a class 1 new Chinese medicine In addition, the recombinant tetravalent human papillomavirus vaccine (6,11,16,18,31,33,35,39,45,51,52,56,58,59) (insect cell) declared for Beijing nuoling biotechnology was selected for priority review time and batch consistent with Chongqing Qiuwen jnsw10032, and the reason for selection was "major special project" (2) Application for production: the approval rate is 21.54% In the review of 23 varieties, 65 new drug acceptance numbers of Hengrui, hausen and Baiji Shenzhou heavy weight drugs are listed for production, including 14 approved, with the approval rate of 21.54% Among the drugs in progress, 20 acceptance numbers are API applications, 31 Acceptance numbers (23 varieties) are preparations, and the following table shows the class 1 new drug preparations under review and approval Among them, Hengrui's carrelizumab for injection, ramtazolam mesylate for injection, hausen's flumatinib mesylate tablets, pegylated losenapeptide injection, and Baiji Shenzhou's zambutini capsule are worth looking forward to 2.2 generic drugs 2.2.1 the main reasons for the approval of generic drugs included in the priority review are first generic products, collinear products, children's drugs, drugs with obvious treatment advantages compared with the existing treatment methods, drug production applications one year before the expiration of the patent, generic drugs that the applicant voluntarily withdraws and re applies after being improved according to the standards consistent with the quality and efficacy of the original research drugs, etc At present, there are 315 acceptance numbers of generic drugs included in the priority review The main applications are production application, with 313 numbers 84 acceptance numbers have been approved, 71 of which are production approval and 13 are clinical approval, with a total approval rate of 26.84% The number of clinical applications is only 2 acceptance numbers, one of which has been approved 2.2.2 in terms of the number of application acceptance numbers (including APIs) of the applicant enterprises, Zhejiang Huahai has the largest number of applications, reaching 37, followed by dongyangguang and Qilu pharmaceutical Here is a brief look at the specific application of the first three enterprises Zhejiang Huahai Zhejiang Huahai has 37 acceptance numbers included in the priority review, all of which are applied for production Among them, 5 are API acceptance numbers, including entecavir, sirodoxin, eferene, donepezil hydrochloride monohydrate and aripiprazole Only eferene has been approved for production There are another 32 acceptance generic drugs, involving 14 varieties At present, 3 varieties are approved for production, including donepezil hydrochloride tablets, valsartan tablets and voriconazole tablets 2 varieties are approved for clinical use, including duloxetine hydrochloride enteric coated capsules and valsartan hydrochlorothiazide tablets In addition, the "enterprise withdrawal" is shown in the celodexin capsule 8 varieties are under review, as shown in the figure below Dongyangguang Pharmaceutical Co., Ltd has 28 acceptance numbers of generic drugs reported for production, among which 4 acceptance numbers are APIs, including moxifloxacin hydrochloride, levofloxacin, esomeprazole magnesium and olmesartan ester 24 are preparations, involving 14 varieties, of which 3 varieties are approved for production, including moxifloxacin hydrochloride tablets, clarithromycin tablets, clarithromycin sustained-release tablets; in addition, levofloxacin tablets show "issued"; currently, 10 varieties are still under review and approval, as follows: Qilu pharmaceutical Qilu pharmaceutical has 22 Acceptance numbers included in the priority review, one of which is the API Application and imatinib mesylate The remaining 21 acceptance No involves 10 varieties of preparations, among which 3 varieties have been approved for production, including olanzapine tablets, Latan Timo eye drops and gefitinib tablets; 3 varieties have been approved for clinical use, including tacrolimus eye drops, chlorteprenomycin eye drops and brinzolamide eye drops; and 4 varieties are under review, as shown in the following figure: 2.2.3 registration classification Among the generic drug registration categories, new registration categories 3 and 4 are the main ones, among which 82 are declared according to category 3, accounting for 26.03%; 164 are declared according to category 4, accounting for 52.06% Since the release of No 51 document in 2016, the registration of chemical drugs has been greatly improved Among the generic drugs, three categories of drugs are the most affected The current definition of three types of chemical drugs is that the domestic applicant imitates the original research drugs that are listed overseas but not listed in China (such drugs should be consistent with the quality and efficacy of the original research drugs) Therefore, the three categories of drugs included in the priority review are also likely to become the first batch with advantages in the competition Three kinds of generic drugs (1) applied for clinical application: 2 drugs were included, 2 accepted drugs in the approved clinical application of 1 drug were included in the priority review, which are chloral hydrate rectal solution of Xinjiang tefeng Pharmaceutical Co., Ltd and sophibuvir, the API of Shanghai Hequan Pharmaceutical Co., Ltd at present, sophibir has been approved for clinical application (2) Application for production: the approval rate is 10% There are 80 production acceptance numbers of Hengrui, Renfu and Zhengda Tianqing three pharmaceutical strength enterprises At present, 8 acceptance numbers have been approved, and the approval rate is 10% Among them, 7 acceptance No 5 varieties are approved for production, including lakoshalamine tablets from Qingfeng, Jiangxi, lamivudine tenofovir tablets from Baker biology, temozolomide for injection from Hengrui pharmaceutical, flurbiprofen ester injection from Da'an pharmaceutical, Chengdu Yuandong biopharmaceutical, and 1 acceptance No 5 variety is approved for clinical use, which is aripiprazole oral solution from Dazhong pharmaceutical, Sichuan Liquid Among the remaining acceptance numbers still under review and approval, 26 are API acceptance numbers; 46 are preparations, involving 33 varieties, as shown in the figure below; Jiangsu Hengrui has the most varieties, 5 of which are Yichang humanwell and Zhengda Tianqing 2.3 imported drugs 2.3.1 the main reasons why the application for approval is generally listed in the priority review are: rare disease drugs, children's drugs, tumor drugs, drugs urgently needed in clinical, new drug forms, new indications, new varieties with obvious treatment advantages compared with the existing treatment methods, etc., which are all relatively needed drugs in China There are 263 import application acceptance numbers included in the priority review, of which 158 are applied for production At present, 104 acceptance numbers are approved, with the approval rate of 65.82% The number of clinical applications is 105 At present, 26 clinical applications are approved and 32 imported applications are approved The total approval rate is 55.24% The production reporting and clinical approval rates of import applications are more than half, which are related to new drugs