Hengrui pyrrolidine is approved for listing! Consistency evaluation of three class 1 new drugs and six over 1 billion injections

The highlights came a few days ago when Hengrui pharmaceutical released its 2018 semi annual report The company's operating revenue was 7.761 billion yuan, an increase of 22.32% year-on-year; the net profit attributable to the parent company was 1.91 billion yuan, an increase of 21.4% year-on-year The company's R & D investment has reached a new high Several heavy new drugs have entered the harvest period 19K has been approved for production Pyrrolidine is in the "approval completed - to be certified" It is reported that the product has been officially approved for listing, and three new drugs of category 1, including PD-1, have been reported for production In the field of generic drugs, it is reported that many first generic drugs have been approved for listing in the reporting period, the first variety has passed the consistency evaluation, and 12 varieties are applying for the consistency evaluation, 7 of which are injections (6 of which have a national sales volume of more than 1 billion yuan in 2017) Through the same production line's overseas reporting to China, the company is expected to take the lead in the consistency evaluation of injections Figure 1: performance of Hengrui pharmaceutical in the same period from 2015 to 2018 (unit: 100 million yuan) (source: semi annual report of listed companies) According to the semi annual report of Hengrui pharmaceutical in 2018, the company's operating revenue and net profit achieved stable growth, with an increase of more than 20% year-on-year The continuous listing of R & D products, the export of preparations and the optimization of existing product structure are the three factors that continuously promote the company's performance growth in the reporting period   none="shifuMouseDownStyle('shifu_bus_002')" style="margin: 1em auto; padding: 0px; max-width: 100%; font-family: -apple-system-font, Bl inkMacSystemFont, "Helvetica Neue", "PingFang SC", "Hiragino Sans GB", "Microsoft YaHei UI", "Microsoft YaHei", Arial, sans-serif; font-size: 17px; letter-spacing: 0.544px; widows: 1; line-height: 25.6px; color: rgb(62, 62, 62); border-style: none none solid; text-align: center; border-bottom-width: 1px; border-bottom-color: rgb(0, 0, 0); box-sizing: border-box !im portant; word-wrap: break-word !im portant; "> R & D investment has reached a new high, and heavy new drugs have been delivered successively According to the company's semi annual report, in the first half of 2018, the company's R & D investment was 995 million yuan, an increase of 27.26% year-on-year, and the proportion of R & D expenses in total operating revenue was as high as 12.82%, an increase of about 0.5 percentage points compared with the same period last year, which continues to be at the domestic leading level High input leads to high output During the reporting period, the company's first biological innovative drug, thiopefigeristine injection (19K, trade name aido), was approved for production Aido is mainly used for chemotherapy-related neutropenia in cancer patients It pegylates granulocyte colony stimulating factor (g-gsf) on the basis of the company's pefigeristine (trade name neulasta) G-gsf is the first drug for neutropenia related to radiotherapy and chemotherapy, including short-acting g-gsf and long-acting g-gsf From the perspective of domestic and foreign markets, long-acting G-CSF has a significant growth rate, and the replacement of short-acting g-gsf is just around the corner Figure 2: brand competition pattern of pegylated recombinant human granulocyte stimulating factor in China's public medical institutions in 2017 (minenet China's public medical institutions terminal competition pattern) According to the data of mienei.com, in recent years, the sales volume of long-term G-CSF has grown rapidly In 2017, the sales volume of terminals in China's urban public hospitals, county-level public hospitals, urban community centers and township hospitals (referred to as China's public medical institutions) was 1.047 billion yuan, an increase of 399.14% over the previous year Amgen's long-term G-CSF pefigstein has been listed in the United States, Japan, the European Union and other countries and regions, but not in China At present, there are two long-term G-CSF products listed in China, jinyuli of Baike biology under PetroChina and xinruibai of Qilu pharmaceutical The sales volume of xinruibai of Qilu pharmaceutical has been increasing year by year since it was listed in 2015, and its market share in 2017 has exceeded that of jinyuli of Baike biology under PetroChina This time, Hengrui pharmaceutical 19K was approved for production, and the long-term G-CSF will present a "tripartite confrontation" situation in the domestic market Table 1: Hengrui pharmaceutical and some of its subsidiaries' new drugs under research (source: minenet global drug R & D base) entered the harvest period of innovative drugs in 2018 According to minenet data, in addition to the 19K that has been approved for production, the listing application of pyrrolidine has been in the stage of "approval completed - to be certified" In addition, the company has three listing applications of class 1 new drugs It is in the stage of "in the review and approval", including cadefloxacin, ramazolam toluene sulfonate and camrelizumab injection (PD-1) Pyrrolidine, a small molecule new drug for breast cancer, was approved for clinical application in May 2012 and declared for production in August 2017 On September 26 of the same year, pyrrolidine was included in the priority review by CDE for the reason of "significant clinical value, major special project" It is a class 1.1 EGFR / HER2 inhibitor independently developed by Hengrui pharmaceutical Currently, the indications applied for are HER2 positive metastatic / advanced breast cancer, HER2 mutant advanced non-small cell lung adenocarcinoma At present, the listing application of pyrrolidine is in the state of "approved - to be certified" According to the person familiar with the matter, the product has been officially approved for listing According to the data of 2017 annual report, Hengrui has invested about 520 million yuan in the research and development of pyrrolidine and tablets Camrelizumab injection (PD-1) entered phase III clinical practice in April 2017 In April this year, its listing application was accepted by CDE and entered the priority approval, which is currently in the "review and approval" At present, there are 2 types of PD-1 on the market in China, namely, Shi Guibao's navumab (trade name Opdivo) and MSD's pemumab (trade name Keytruda) The global sales volume of Opdivo in 2017 is US $4 billion 948 million, and that of Keytruda in 2017 is US $3 billion 908 million Rimazolum toluenesulfonate entered phase III clinical practice in August 2017 In March this year, its listing application was accepted by CDE, and was included in the priority review process in April Currently, it is in the process of "review and approval" Ramazolam, a short acting GABA-A receptor agonist, is a super quick acting sedative / anesthetic and can be used as an operative anesthetic In addition, shr3680 tablet successfully entered the phase III clinical, which is an AR receptor antagonist, intended to be used in the treatment of prostate cancer that failed to castrate or failed to use traditional hormone therapy At present, five ar antagonists, bicalutamide (the first generation), enzalutamide (the second generation) and apalutamine (the new generation), have been listed in the world, while only the first generation of AR antagonists in China has been approved for listing   none="shifuMouseDownStyle('shifu_bus_002')" style="margin: 1em auto; padding: 0px; max-width: 100%; font-family: -apple-system-font, Bl inkMacSystemFont, "Helvetica Neue", "PingFang SC", "Hiragino Sans GB", "Microsoft YaHei UI", "Microsoft YaHei", Arial, sans-serif; font-size: 17px; letter-spacing: 0.544px; widows: 1; line-height: 25.6px; color: rgb(62, 62, 62); border-style: none none solid; text-align: center; border-bottom-width: 1px; border-bottom-color: rgb(0, 0, 0); box-sizing: border-box !im portant; word-wrap: break-word !im portant; "> another product was first imitated and listed in the United States, and the export of preparations was retransmitted to Jiebao On March 2, Hengrui pharmaceutical released a notice that its subsidiary Shanghai Hengrui's application for simplified new drug of desflurane for inhalation (anda) has been reviewed and approved by FDA and can be listed and sold in the United States At present, in the U.S market, Hengrui is the first enterprise to declare the generic drugs of this variety, in addition to the original research manufacturer, Baite Desflurane is suitable for anesthesia induction and / or maintenance of adult inpatients and outpatients, as well as anesthesia maintenance of infants and children Desflurane (trade name: Youning), the original manufacturer of American Baite, was approved by FDA for sale in 1992 and has been listed in China, EU, Japan, South Korea and other countries and regions According to the data of mienei.com, in 2017, the sales volume of desflurane for terminal inhalation in public medical institutions in China was close to 100 million yuan Table 2: during the reporting period from January 2018 to now, Hengrui and its subsidiary anda have been approved (source: announcement of listed companies) During the reporting period, Hengrui pharmaceutical and its subsidiary have obtained 4 new anda in the United States (one is temporarily approved), with a total investment of RMB 171.29 million, of which 2 are the first ones in China, including desflurane for inhalation and fondaparinux injection Hengrui Pharmaceutical Co., Ltd announced on August 7th that its subsidiary, Shanghai Hengrui, recently received the "drug registration approval" issued by the State Drug Administration for halothane used for inhalation At present, in the domestic market, Hengrui is the first enterprise to apply for the generic drug in addition to the original research manufacturer, Baite, USA In addition, Hengrui's application for the production of desflurane for inhalation was included in the priority review procedure for the reason of "production in the same production line, listing in the European Union in 2017" For this approved production, Hengrui medicine only needs to submit a supplementary application for conformity assessment Once passed, it can use the conformity assessment mark and enjoy the policy dividend Hengrui medicine obtained the Anda batch number of fondaparinux injection on May 18, 2018, which can be produced and sold in the United States Before that, Hengrui pharmaceutical has submitted the listing application to the State Drug Administration and included it in the priority review On May 31, Hengrui pharmaceutical received the approval document for drug registration issued by the State Drug Administration, and the sulfondagangui sodium injection has become the first one in China Fondaparinux injection was developed by mylan Ireland Ltd., an American company It was first approved for marketing by FDA on December 7, 2001 In 2009, British Glaxo Group Ltd's artixtra (Android) was approved to be listed in China, and changed to Ireland Aspen Notre Dame de bondeville's artixtra (Android) in 2015 In addition to Hengrui pharmaceutical, several domestic enterprises, such as Zhengda Tianqing, Tianjin HongRi, Xintai pharmaceutical and Liaoning hisic, have submitted six kinds of applications, and no enterprises have been approved yet   none="shifuMouseDownStyle('shifu_bus_002')" style="margin: 1em auto; padding: 0px; max-width: 100%; font-family: -apple-system-font, Bl inkMacSystemFont, "Helvetica Neue", "PingFang SC", "Hiragino Sans GB", "Microsoft YaHei UI", "Microsoft YaHei", Arial, sans-serif; font-size: 17px; letter-spacing: 0.544px; widows: 1; line-height: 25.6px; color: rgb(62, 62, 62); border-style: none none solid; text-align: center; border-bottom-width: 1px; border-bottom-color: rgb(0, 0, 0); box-sizing: border-box !im portant; word-wrap: break-word !im portant; "> the first consistency evaluation variety was born, and 12 varieties were on the way On August 3, Hengrui pharmaceutical announced that the company recently received the approval document for supplementary application of ambroxol hydrochloride tablets (trade name Belle) issued by the State Drug Administration Belle is the first consistency evaluation variety declared by the company and the first variety passed the consistency evaluation Ambroxol hydrochloride tablets are expectorants, which can be used for the treatment of acute and chronic respiratory diseases, abnormal bronchial secretion, etc it was developed by Berlin Ingelheim company in Germany and approved to be listed in Germany in 1979 According to the data of minenet, in 2017, the sales volume of ambroxol hydrochloride tablets at the terminals of public medical institutions in China was 214 million yuan, ranking first among the top 20 tablet products of expectorants (excluding the compound preparations containing cough medicine) In addition to Hengrui medicine, at present, the main domestic manufacturers of ambroxol hydrochloride tablets are the original research manufacturers, such as bringer Ingelheim, Sandoz pharmaceutical, Shandong Yuxin pharmaceutical, etc The leading company is bringer Ingelheim, with a market share of more than 47% in 2017 Table 3: application for consistency evaluation of Hengrui pharmaceutical and its subsidiaries (source: minenet database, statistics as of August 14, 2018) according to minenet Med China drug review database 2.0