Biological similar medicine ushers in a new era! Who is the first to win in the research and development of six monoclonal antibody analogues in China?

In 2016, among the top 10 drugs in the world, there are 7 biological drugs, 6 of which are monoclonal antibodies Xiumeile, the king of monoclonal antibodies, has a sales volume of US $16 billion, while Roche's top three monoclonal antibodies have a total sales revenue of US $20.6 billion, accounting for 53% of Roche's drug revenue In the face of such temptation, the research and development of biological similar drugs are booming in the world Compared with the chemical generic drugs, the research and development barriers of biological similar drugs are higher and the price reduction rate is lower (10% ~ 35%), so it can obtain larger market and higher profits According to the forecast, the global market size of bio similar drugs in 2020 will be US $35 billion From a global perspective, at present, the research and development of biological similar drugs are mainly in EPO, growth hormone, rituximab, trastuzumab, bevacizumab, adalimumab, etanercept and infliximab and other large varieties with expired patents However, due to the high R & D threshold of biological similar drugs, participants are concentrated in a few giants such as Novartis, hospita, Amgen, MSD / Samsung In China, 2015 is a turning point for the management of biological similar drugs The regulations of similar drugs are clear and in line with Europe and the United States, which directly and greatly improves the barriers of research and development and production, while protecting the market At present, Fuhong Hanlin, Xinda biology and other enterprises have made rapid progress in research and development, and have been in the forefront of research and development of biological similar drugs According to the forecast, 2015-2020 will be the stage of global bio similar drugs ushering in the growth At this stage, what will be the pattern of global bio similar drugs? Who will be the winner among Chinese bio similar drug players? 1 similar drug market is coming In 2016, biological drugs accounted for 44% of the world's top 200 drug sales Monoclonal antibody is the largest category According to the global top 200 drug sales data in 2016, there are 70 biological drugs with a total amount of US $157.2 billion, accounting for 44%; monoclonal antibodies (including recombinant protein etanercept with similar characteristics and monoclonal antibodies, the same below) are the largest category with a total amount of 26, with a total amount of US $86 billion, accounting for 55% of the proportion of biological drugs Among the 26 McAbs, 6 McAbs and recombinant protein products with the largest sales volume are adalimumab, enacept, infliximab, rituximab, bevacizumab and trastuzumab, with a total amount of 53.842 billion US dollars, accounting for 63% of the McAb market Compared with foreign countries, there is a big gap in the sales of biological drugs in China The sales of three single anti bevacizul drugs, rituximab and trastuzumab in 2016 are all about 2 billion yuan, with big difference and low permeability Many of the heavyweight biopharmaceuticals are on the verge of maturity, and a large market for similar drugs is coming 2017-2020 will be the golden stage of the development of biological similar drugs: 2013-2015 is mainly the concentrated expiration time of non monoclonal antibody biological drugs, and generic drugs of long hormone, erythropoietin, granulocyte colony stimulating factor, interferon, insulin and other products will be listed successively; 2016-2020 is the peak of patent expiration of monoclonal antibody, including adamutumab The patents of infliximab, rituximab, bevacizumab and trastuzumab have expired in recent years (Europe, the United States), and the market of biological similar drugs is coming The world's approved bio similar drugs are concentrated in growth hormone, erythropoietin, granulocyte colony stimulating factor, adalimumab, infliximab, rituximab and other large varieties whose patents have expired, of which 21 are approved by the European Union and only 5 are approved by the United States with more strict and cautious regulation At present, the sales volume of five biological similar drugs in the United States is very small due to patent lawsuits or non interchangeability In the future, it mainly depends on three varieties, i.e Amgen adamumumab similar drugs (approved in September 2016, not yet sold), infliximab (approved in February 2016) and sandostasip (approved in August 2016) 21 approved similar drugs in Europe are mainly growth hormone, erythropoietin, granulocyte colony stimulating factor, adalimumab and other large varieties of monoclonal antibodies were less approved, of which the infliximab of hospitara / celltrion became the first approved monoclonal antibody similar drug in the European Union (September 2013) Compared with general chemical drugs, biological similar drugs are more difficult, more expensive and have a longer cycle Players participating in similar drug market competition are concentrated in a few giants such as Novartis, Pfizer, Amgen and MSD The R & D pipelines of five international similar drug giants, namely, Novartis, hospitra, celltrion (South Korea), Amgen and MSD / Samsung, are currently listed in four similar drugs and six are under research Pfizer entered the competitive market of bio similar drugs after its US $17 billion acquisition of hospita in 2015 At present, Pfizer has two varieties on the market and seven are under research Jin is a leader in the biological medicine industry, and does not relax in the similar medicine market At present, there are 1 variety on the market and 7 under research Korean enterprises occupy a more important position in the Asia Pacific region and even in the global market of biological similar drugs Celltrion and Samsung bioepis (MSD cooperative enterprise) are the top two companies in terms of the number of biological similar drugs on the market At present, celltrion has three varieties on the market, five under research, and Samsung bioepis (MSD cooperative enterprise) has three varieties on the market, four under research It can be seen from the analysis of the research pipelines of major companies that the research and development of similar drugs are concentrated on the patent expiring large varieties of monoclonal antibodies such as adalimumab, infliximab, rituximab, bevacizumab, trastuzumab, etc., while the research and development of recombinant protein drugs such as non gristin and insulin are less In the future, the research and development of monoclonal antibody analogues will remain a hot spot, with attention paid to domestic research and development enterprises of monoclonal antibody analogues In addition, as governments control the growth of medical and health costs and the wave of expiry of biopharmaceutical patents in 2015-2020 strikes, the growth of biopharmaceutical analogues is at a high speed According to IMS data, it is predicted that by 2020, 20% of the price reduction of eight major bio similar drugs will save us $4.9 billion in medical expenditure, and if the decrease reaches 40%, it will save us $9.8 billion in medical expenditure In 2020, the global market space for bio similar drugs will reach US $35 billion, and the CAGR from 2013 to 2020 will reach 60.8% 2 The barriers to the research and development of bio similar drugs in China have been raised The regulation of bio similar drugs is unclear The first generation of recombinant protein generic drugs are many and the competition is poor Growth hormone, EPO, GCSF and other first generation bio drugs were widely used in China in 2004 The low price and vicious competition resulted in the failure to breed heavy varieties Taking EPO as an example, in 2015, the global sales volume was US $2.939 billion, but the total domestic sales volume was less than 1 billion In 1992, imported products entered China for the first time, but at that time, due to the low barriers of domestic biological drug research and development, nearly 20 enterprises, including Sansheng Pharmaceutical (1998), Shandong Ahua, Nanjing Huaxin, etc., received the EPO approval The market presents a situation of many generic drugs and vicious price competition No single enterprise's EPO varieties have become the heavyweight varieties that have sold more than 1 billion In 2015, the laws and regulations of biological similar drugs in China are clear, the barriers to entry of the industry are greatly increased, and the research and development of monoclonal antibody will move from innovation declaration to similar drug declaration, and it will be a market for a few players in the future With the improvement of similar drug laws and regulations, the application of McAbs for new drugs may be a thing of the past The requirements of the original research head for head design tests have greatly increased the requirements for research and development capacity, research and development costs, production technology, and the barriers to entry of the industry The administrative measures for drug registration (2007) requires that "biological products should be declared according to the procedure of new drug application" In the past, most of the approved monoclonal antibody drugs in China were declared according to new drugs The clinical trial and approval process was very long, but the overall cost was not high Since the release of technical guidelines for research and development and evaluation of biological similar drugs (Trial) in February 2015, regulatory authorities have given clear guidance on the definition and research and development of biological similar drugs In July 2016, the measures for the administration of drug registration (Revised Version) standardized the concept of biological similar drugs In Article 77, it was proposed for the first time that "when approving drugs, attention should be paid to the similarity between the quality and efficacy of biological similar drugs and the original drugs", and it was also proposed that“ Article 90 in case of any of the following circumstances, the examination and approval department shall make a decision of disapproval in accordance with the law: (7) for a drug registration application that is not identical with the structure of a domestic listed biological product, or changes its clinical characteristics, preparation characteristics, cell matrix, etc., the applicant is unable to prove its technical innovation and its clinical value has obvious advantages over the original variety; (8) there are already The comprehensive evaluation of the registration standard of biological products with similar products listed in China is lower than that of the products already listed " These two regulations have raised the threshold of research and application of biological similar drugs On March 1, 2017, the National Pharmacopoeia Committee issued a notice on Soliciting Opinions on the rules for naming common names of biological products, regulating the method of common names of biological products (inn) Domestic enterprises that conduct product research and development and clinical trial design in strict accordance with the standards of biological similar drugs, as long as they pass the clinical trial, can enjoy the same common name as the original research drug when they go on the market, consider extrapolating the indications of the original research, and share the huge market of the original research drug In addition, the entry of McAbs into the medical insurance negotiation catalogue also provided strong support for the development of similar biological drugs in China, and accelerated the speed of market introduction and volume On April 14, 2017, the Ministry of human resources and social security issued the Circular of the general office of the Ministry of human resources and social security on determining the negotiation scope of the national basic medical insurance, work injury insurance and maternity insurance drugs catalogue in 2017, which identified 44 negotiated drugs lists Among them, there are 7 McAbs, which show the full recognition of the relevant departments of medical insurance for the clinical value of McAbs; the three swordsmen of Roche's anti-tumor McAb - trastuzumab, rituximab and bevacizumab are all included in the negotiation list If the negotiation is successful, its price will have a very important impact on the medical insurance payment price of bio similar drugs in the future The price of domestic bio similar drugs listed in the later stage will take this price as a reference, which is expected to enter the medical insurance directly, which is conducive to the acceleration of market access and the rapid volume after listing Who is the first to win? Domestic monoclonal antibodies are concentrated in 6 categories of products, such as rituximab, trastuzumab, bevacizumab, etc., with less application for biologically similar drugs and more application for new drugs At present, the research and development of biological drugs in China mainly focus on rituximab (non Hodgkin's lymphoma), trastuzumab (breast cancer), bevacizumab (colorectal cancer), adalimumab (rheumatoid arthritis, mandatory spondylitis), etanercept (rheumatoid arthritis) and infliximab (rheumatoid arthritis) Most of the major products are new drugs declared according to the old laws and regulations, and few products are declared according to similar drugs Rituximab: when the patent expires, the sales volume of generic drugs in the non-standard market will increase, and the overall sales volume will decline When the patent expires, the sales volume of rituximab will decline, and only truxima is the similar drug in the standard market Rituximab is a chimeric monoclonal antibody against CD20 developed by Roche (Genentech / Chinese and foreign pharmaceutical) and Baijian It is mainly used in non Hodgkin's lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis It was approved by FDA on November 26, 1997, and entered China on April 21, 2008, under the trade name of rituxan / rituxan As Rogowski monoclonal antibody