Ddp-4 imitation war is not ready: a large number of generic drugs will be on the market by 2023

Source: influenced by the consistency evaluation and the change of drug registration laws and regulations, pharmaceutical enterprises in China are generally faced with the problem of how to choose the direction of R & D project approval China's clinical approval documents of drugs have been approved in batches since 2015, so after full evaluation, high-quality projects will start clinical trials In 2016, the number of clinical trials of diabetes related drugs declined: there were 82 clinical registration numbers in 2013, 42 in 2014 and 54 in 2015, compared with 28 in 2016 (as of October 17, 2016) Among them, the main target of registration is type 2 diabetes In 2016, 82% of the indications for clinical registration of diabetes drugs in China were type 2 diabetes, 71% in 2015 and 74% in 2014, all of which were over 70% However, the indications of diabetic neuropathy and diabetic nephropathy are rarely registered In 2016, 83% of the drugs declared as type 2 diabetes test drugs were dipeptidyl peptidase-4 inhibitors (ddp-4 inhibitors) Ddp-4 inhibitor can selectively inhibit the hydrolysis of GLP-1 (glucagon like peptide-1) and GIP (insulin stimulating peptide-1) by ddp-4, increase the plasma concentration of active intestinal glucagon, and thus reduce blood glucose At present, the approved ddp-4 inhibitors are hot spots in the research and development of diabetes drugs in China because they only need to be taken once a day and the patients have good compliance It will take a long time for foreign enterprises to monopolize the domestic independent R & D of two varieties that have been listed At present, only the original manufacturers of ddp-4 inhibitors are foreign enterprises This is related to the clinical self inspection launched by FDA on July 22, 2015 Jiangsu Hengrui's class 1.1 new drug, repagliptin phosphate tablets, was the most likely drug to break the monopoly situation of foreign enterprises in ddp-4 inhibitors, but it finally withdrew its production application in 2016 and restarted phase I clinical trials Hengruiruigliptin tablets were approved for clinical use in 2009, and declared for production in 2015 This means that it will take at least five years for Hengrui's repagliptin phosphate tablets to be successfully marketed in China In addition, in July 2015, Chengdu Yuandong Pharmaceutical Co., Ltd was approved as a class 1.1 new drug, ugletin tablet, and started phase I clinical trial in West China Hospital of Sichuan University in 2016 In 2014, egletin tartrate tablet of Shandong green leaf, which was approved for clinical use, has not found the information of starting phase I clinical trial Fugliptin benzoate capsules transferred by Shenzhen xinlitai from Chongqing fuchuang technology are still in phase I clinical stage in 2015 In terms of the application for generic drugs of the hottest imitated and declared varieties of agliptin benzoate and tragliptin succinate, agliptin benzoate tablets and tragliptin Succinate Tablets are the hottest ddp-4 inhibitors in China at present, followed by cigliptin phosphate tablets In April 2010, agliptin benzoate tablets were first approved by the Japanese market, and the earliest clinical application of generic drugs in China can be traced back to 2011, which shows the enthusiasm of Chinese R & D enterprises to rush for the application of generic drugs The original compound patent applied by agliptin in China was rejected, which made domestic enterprises feel that it is possible to obtain approval in advance, so research and development enterprises are more active in applying However, after the original manufacturer's patent was rejected, several patent divisions with simplified claims were applied in China Each patent division covers the claims of agliptin benzoate separately It is expected that the patent will expire in 2024 In 2016, Yabao pharmaceutical launched the bioequivalence test of agliptin benzoate tablets, which is the only one at present The bioequivalence test was carried out in the first hospital of Jilin University If the patent expiration time is strictly considered in the future drug registration and approval in China, the earliest time to market of agliptin benzoate tablets will be 7 years Tragliptin Succinate Tablets, developed by Takeda, is the first long-acting DPP-4 inhibitor approved for market in the world, and the market time is March 2015 Takeda, the original manufacturer of trogliptin Succinate Tablets, is not listed in China and has not carried out clinical trials Trogliptin Succinate Tablets are also facing the situation that compound patents are rejected and patent cases are pending in China It is expected that the patent will not expire until 2024 at the earliest At present, there are 28 domestic manufacturers applying for clinical application of trogliptin Succinate Tablets Home, including Beijing kanglisheng, Beijing shenlanhai, Beijing Wansheng, Chengdu Beite, Chengdu Yuandong, Dongguan Changan East sunshine, Guangzhou egger, Guangzhou Baiyunshan Guanghua, Guizhou Hengshun, Hangzhou Huadong pharmaceutical, Hefei Tuorui, Jilin 4th ring, Beijing aohe, Jiangsu Haosen, Jiangsu kefeiping, Nanjing Wanchuan, Nanjing Zhengda Tianqing, Qilu pharmaceutical, Ruiyang pharmaceutical, Shijiazhuang Siyao, Sinopharm group, Sichuan Kelun, Sichuan xinston, Tianjin hankang, Tonghua Dongbao, Hong Kong Jiuhua Huayuan, Zhejiang Haizheng, Zhengda Tianqing and Chongqing Institute of medical technology are in fierce competition The earliest declaration time is November 2015 Some products of ddp-4 inhibitors that have been listed in China are facing patent cliff The patents of vigletin in 2019, sagletin in 2021, sigletin in 2022 and ligletin 2023 expire In 2016, two manufacturers of viagliptin tablets have started the bioequivalence test for human body, including Beijing Taide Pharmaceutical Co., Ltd and Jiangsu Haosen Pharmaceutical Co., Ltd., with a target number of 48 people The former started the project in the first hospital of Jilin University, and the latter started the project in the first hospital of Lanzhou University and Shanghai drug metabolism research center At present, only Jiangsu aosaikang Pharmaceutical Co., Ltd has carried out the bioequivalence clinical trial of shagliptin tablets in Chinese healthy subjects in 2016, which is in the charge of Beijing Shijitan Hospital Affiliated to Capital Medical University In addition, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd also launched the bioequivalence test of Shah Glenn Dean capsule in human body, which was also carried out in No.1 Hospital of Jilin University Tigletin, whose patent expires in 2012, has not yet been listed in China In 2016, Tianbian Mitsubishi Pharmaceutical Co., Ltd launched phase III clinical research, mainly focusing on the effectiveness and safety of Chinese patients with type 2 diabetes Sichuan Kelun Pharmaceutical Co., Ltd conducted bioequivalence study on xigliptin phosphate tablets in Gulou Hospital Affiliated to Nanjing University Medical College in 2016, with the application specification of 100mg / tablet There is no domestic enterprise to carry out clinical application of liggliptin Summary: by analyzing the application of diabetes drugs in clinical trials from 2013 to now, we can see that in the short term, the generic competition of ddp-4 inhibitors is mainly the competition between the original drug manufacturers With the expiration of the original research drug patent, ddp-4 inhibitor generic drugs are expected to be listed in 2019 as soon as possible, and the competition between the first manufacturer and the original manufacturer is mainly oligarchic in 2019-2023 There will be a large number of generic drugs on the market around 2023 The class 1.1 new drugs under research in China are also expected to be listed around 2023, which will further intensify the market competition.