The research and development costs of these 8 domestically produced new drugs have exceeded 100 million yuan

For a long time, the pharmaceutical industry has a "double decade" for R & D investment in new drugs, that is, it will take at least ten years and one billion dollars In fact, it's almost 10 years old According to the latest analysis report released by Deloitte, the cost of successfully listing a new drug has increased from US $1.188 billion in 2010 to US $2 billion in 2017 (see: Deloitte: the return on investment in new drug research and development is only 3.2%, and it takes us $2 billion to market a new drug) In the past two years, the development of new drugs in China is also a hot wave The bio analogues continue to make bubbles The target of PD1 is surrounded by hundreds of game player The number of China clinical trials of Frontier therapy CAR-T is surpassing that of the United States Although from the figure of R & D cost, Chinese pharmaceutical enterprises in the initial stage of innovation have no direct comparability with international giants, but they have paid more and more attention to R & D, and the enterprises willing to spend a lot of money on R & D layout in the early years have either successfully transformed into innovative pharmaceutical enterprises, or have widened the gap with their domestic counterparts However, new drug research and development is definitely a matter of high investment, long cycle and high risk It's better to provide some figures directly to prove it than to put out a set of old sayings here Let's take a look at the domestic R & D cost of more than 100 million products At present, more than 100 million yuan of domestic new drugs (part) are invested in R & D: the company has publicly disclosed information 01 pyrrolidine maleate tablets Hengrui medicine pyrrolidine maleate is an oral, irreversible, pan erbB receptor tyrosine kinase inhibitor (TKI) developed by Hengrui, and it also has anti EGFR / HER1, HER2 And HER4 activity, also known as oral Herceptin, is a new drug project that Hengrui hopes for At present, there are 9 clinical trials registered in China, involving three indications: HER2 + advanced or metastatic breast cancer, HER2 + advanced NSCLC and HER2 + advanced gastric cancer Among them, the development progress of breast cancer indications is the fastest, and it has entered phase III clinical In the phase II clinical trial for breast cancer patients who failed to receive anthracycline and Taxus drugs and received chemotherapy no more than 2 lines after relapse / metastasis, the objective response rate of pyrrolidine + capecitabine (hereinafter referred to as "pyrrolidine group") was 78.5%, and that of rapatinib + capecitabine (hereinafter referred to as "rapatinib group") was 57.1% Compared with lapatinib group, the objective remission rate of pyrrolidine group was increased by about 21% The median PFS was 18.1 months in the pyrrolidine group and 7.0 months in the lapatinib group The risk of disease progression and death was reduced by 63.7% in the pyrrolidine group Pyrrolidine maleate is a fast way to declare Hengrui applied for the first time in May 2011 and was approved for the first time in May 2012 It is in view of the excellent phase II clinical data above that Hengrui submitted the conditional listing application of pyrrolidine for breast cancer treatment to CDE On August 24, 2017, it was accepted by CDE and took the special approval channel On September 26, 2017, it was included in the priority review by CDE for the reason of "significant clinical value and major special project" At present, the technical review of the clinical part has been completed, and the pharmaceutical and pharmacological toxicology parts are queued for review, which is expected to obtain CFDA approval in 2018q2 As of December 2017, Hengrui has invested about 520 million yuan in the research and development of pyrrolidine maleate and tablets In the follow-up, there will be phase III research on lung cancer and gastric cancer indications waiting to burn money It is not a dream that the R & D cost of pyrrolidine will exceed 1 billion yuan Tianshili Compound Danshen dropping pill is a well-known Chinese patent medicine In 1997, it started the process of listing in the United States and passed the FDA's ind application as a drug In 2006, Tianshili reapplied a new ind to FDA and determined the clinical indications for the prevention and treatment of chronic stable angina pectoris The drug code of Compound Danshen dropping pill used in clinical research institute was T89 The phase II clinical trial was prepared from February 2007 Since November 2008, the first group of patients was enrolled into the group Clinical trials involving multiple doses, randomized double blind, multi center parallel control and other aspects were conducted in clinical centers in 11 states, such as Florida, Texas and so on After two years of preparation, the FDA phase III clinical trial of Compound Danshen Dropping Pills (T89) was officially started in August 2012 In the phase III clinical study of T89, a double-blind, randomized, multinational, multicenter, placebo-controlled and double-control clinical design was used to evaluate the safety and efficacy of Compound Danshen Dropping Pill (T89) in patients with chronic stable angina In August 2017, Tianshili released a notice that the point-to-point comparison results of the fourth week were statistically significant, and the actual statistical results of the clinical trial p value was 0.06, which did not meet the requirements of the phase III clinical plan for statistically significant primary observation end-point time of the fourth week Therefore, on the basis of the completed phase III clinical trials, it is necessary to conduct a six week statistical significant clinical trial to meet the new drug application According to the information of TSL's 2016 annual report, the investment in T89 project has reached 372.3 million yuan Compound Danshen dropping pill is the first compound Chinese medicine in the world to apply for FDA new drug listing It is a long-term systematic project with many cutting-edge and originality It is influenced by many factors such as technology, examination and approval, policy and so on There are also many uncertain factors At present, the market has not been successful, and the R & D investment of Compound Danshen dropping pills will continue to increase 03 HLX01 (rituximab analogue) Fuhong Hanlin HLX01 is a biological analogue of rituximab, a heavy bomb drug of Roche, and the first biological drug developed by Fuhong Hanlin According to the medicine cube sales database, Roche's global sales in 2016 reached 7.3 billion Swiss francs, ranking the fifth best-selling medicine in the world However, its patent protection in Europe has expired at the end of 2014, and that in the United States will expire in 2018 At present, it is facing the impact of biological similar drugs In China (excluding Hong Kong, Macao and Taiwan), only rituximab injection of Roche yuanyan is listed According to IMS data, in 2016, the sales volume of meiluohua in China was about 1.5 billion yuan There are more than 10 enterprises in China that have developed and registered the melowa analogues, including well-known enterprises such as Sansheng Guojian, Fuhong Hanlin, Xinda biology, Haizheng pharmaceutical, Zhengda Tianqing, Hualan biology, Lizhu monoclonal antibody, and 5 enterprises such as Wanle pharmaceutical and Shandong new era that have applied for the monoclonal antibody varieties targeted at CD20 The competition is very fierce The application for listing of Fuhong Hanlin rituximab injection in the treatment of NHL (cxss1700026) was officially accepted by CDE on December 11, 2017 After CITIC Guojian's application for the listing of recombinant anti-CD20 mouse chimeric monoclonal antibody injection (cxss1100021) was withdrawn due to clinical self-examination, Fuhong Hanlin became the first one of domestic enterprises to develop rituximab analogues, and is expected to become the first generic drug of rituximab As of September 2017, Fuhong Hanlin has invested 290 million yuan in research and development of HLX01 project 04 hlx02 (trastuzumab analogue) Fuhong Hanlin hlx02 (recombinant anti HER2 humanized monoclonal antibody for injection) is a biological analogue of Herceptin (trastuzumab) developed by Fuhong Hanlin In July 2015, hlx02 obtained the clinical approval of breast cancer indications issued by CFDA At present, breast cancer indications have entered the phase III clinical research stage, and successively obtained the phase III clinical trial licenses of Ukraine, Poland and the Philippines The international multi center research has been carried out in an all-round way In January 2016, hlx02 obtained the clinical approval of gastric cancer indications issued by CFDA As of April 2017, Fuhong Hanlin has invested about 202 million yuan in research and development of hlx02 (including indications for metastatic breast cancer and gastric cancer), which will continue to rise with more phase III clinical trials Haize Mabu tablet Haizheng pharmaceutical Haize Mabu is a 1.1 type of lipid-lowering drug developed by Haizheng pharmaceutical Its mechanism is to inhibit the absorption of food and liver circulating cholesterol by acting on the small intestine brush border transporter npc1li The second Unblinding was carried out on the night of September 18, 2015 in the phase II clinical trial of hs-25 The results showed that there was a statistical difference in LDL-C reduction of 5 mg, 10 mg and 20 mg of hezemab compared with that of placebo group, and the LDL-C reduction rate of 10 mg and 20 mg of hezemab compared with that of the positive control group (mosadong yizhemeb), but there was no statistical difference in the trend of LDL-C reduction There was no significant difference in the severity of adverse events and the incidence of adverse reactions between the two groups As of June 2016, Haizheng has invested about 153 million yuan in the drug R & D project 06 anti her2-adc (arx788) Zhejiang Pharmaceutical recombinant human anti HER2 mab-as269 coupling injection (arx788) is a new generation of monoclonal antibody coupling drug introduced by Zhejiang Pharmaceutical when it signed the cooperation development and license agreement with ambrx company of the United States on June 14, 2013 The main indications to be developed are breast cancer, gastric cancer, etc HER2 target products of the same kind that have been listed abroad are mainly Herceptin, tykerb, perjeta and kadcyla Many domestic enterprises, such as Rongchang biology, Qilu pharmaceutical, Haizheng pharmaceutical and Hengrui pharmaceutical, have obtained the clinical trial approval documents of similar drugs On January 20, 2016, Zhejiang Pharmaceutical submitted the application for clinical trial of the drug to CFDA and was accepted, and obtained the clinical approval document on March 15, 2017 On October 20, 2017, Zhejiang Pharmaceutical first registered and publicized a single center, open and dose increasing phase ia clinical study (ctr20171162) of arx788, to evaluate the safety, tolerance and pharmacokinetic characteristics of arx788 in the treatment of HER2 positive advanced breast cancer, and planned to enroll 21 people Phase I clinical trials of Zhejiang medicine in New Zealand and Australia are under way As of March 2017, Zhejiang Pharmaceutical has invested 125 million yuan in the project, which is far from the stage of burning money 07 at132 (anti TNF α monoclonal antibody) Lizhu monoclonal antibody of Lizhu group obtained the clinical approval document (approval number: 2014l00371) of at132 (recombinant human anti TNF α monoclonal antibody for injection) on February 28, 2014, and was approved to carry out phase I clinical trial, and completed two phase I clinical studies in March 2016, which are mainly applicable to the treatment of rheumatoid arthritis In December 2016, at132 obtained phase II and phase III clinical approval documents issued by CFDA On March 28, 2017, lizumab registered a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial of at132 in the treatment of moderate and severe rheumatoid arthritis It is planned to enroll 150 people At present, the study has not begun to recruit As of September 2017, Lizhu has invested about 110 million yuan in the research and development of the drug Retagliptin 08 phosphate tablets retagliptin is a new class 1.1 me too drug developed by Hengrui, which belongs to DPP-4 inhibitor It can be used to improve the blood glucose control of type 2 diabetic patients in combination with diet control and exercise In June 2015, the listing application of repagliptin phosphate tablets was accepted by CDE, but 722 clinical self-examination happened immediately On April 7, 2017, Hengrui announced the withdrawal of regletin