Analysis of the current situation and trend of the development of new vaccines in China in 2019

The new vaccine has the characteristics of good efficacy, high technical barrier and high returnFrom the demand side, innovative vaccines, multi-linked multi-price vaccine demand is not complete, the public consumption upgrade, the new vaccine is the development trend of the vaccine industry; On November 11, 2018, the State Administration of Market Supervision and Administration announced the Vaccine Administration Law of the People's Republic of China (Draft for Comments), which was promulgated on June 29, 2019 and officially implemented on December 1, 2018The new Vaccine Management Act provides a series of new provisions to encourage the innovation and development of vaccines, support the development of new vaccines such as multi-linked multi-price, and give priority to the review and approval of innovative vaccinesThe speed of launch of new vaccine enterprises in China will be further accelerated, and new vaccine development enterprises will usher in better opportunities for developmentThe world's top 15 varieties generated total sales of $22.4 billion in 2018, accounting for 65% of the total vaccine production value, and Prevnar13 single varieties sales reached $5.802 billion in 2018China's top 15 varieties total sales of 20.6 billion yuan, accounting for 72% of the domestic vaccine output valueMost of these heavyweights are innovative vaccines and multi-linked multivalent vaccinesTable 1 Since 2010, China's vaccine market products Domestic vaccine enterprises research and development of a new generation of vaccines generally began in 2000 onwards, in recent years these products have entered the market stageAfter 2016, the domestic drug review reform initially showed results, the speed of examination of listing applications accelerated, the threshold of the introduction of imported products relaxed, but overseas vaccine enterprises limited production capacity, the supply of Chinese products can not meet the huge demand, to domestic enterprises left a catch-up opportunity, such as HPV vaccine, pneumonia polysaccharide combination vaccineDomestic vaccine enterprises in research projects gradually enter the market, domestic seedlingvariets are becoming increasingly richHib vaccine and its combined vaccine, Haemophilus influenzae type b (Hib) is an important pathogenic bacteria in respiratory diseases in infants and young children, causing diseases such as pneumonia and meningitisHib is resistant to many types of antibiotics, so the Hib vaccine is of great significance in our country, where antibiotic abuse is more commonHib vaccine immune response is good and efficientAmong them, Hib single seedling is a mature product, at home and abroad many similar products and the difference is not bigAnd the joint seed containing Hib can effectively reduce the total vaccination needle, is the domestic and foreign manufacturers keen development fieldAs many as nine manufacturers have supplied Hib vaccines since 2008, but some have produced/developed Hib-group seedlings only, producing small amounts of Hib vaccine spent each year to maintain production permitsThe market is currently supplied by five, with the main suppliers being Watson Bio and Minhai (Kantai) There are three domestic Hib-League miaos, including The AC-Hib Trio of Zhifei, The Baibai Break-Hib-Hib Of-House And Sanofi's Baibai-White-Hib Five-Miao Sanofi's Pan Tae-hsin as the only one listed in china, Baibai-Inactivated Polio-Hib pentatrice, needs only 4 injections to achieve the effect of preventing baibaiburst, polio and Hib, while separate vaccinations require a total of 12 injections Pan Taixin tender price of 599 yuan per needle, 4 injections totalling 2400 yuan, the amount of issuance in 2019 reached 4.2062 million, is expected to be 5 million in 2022, the corresponding market space of 12 billion yuan Figure 1 Number of Hib vaccines and their joint vaccine batch issues 2015-2019 Data source: Central Inspection Institute from the number of batch issues, as of December 22, 2019, China hib single seedlings, AC-hib triple seedlings (Zhifei bio), Baibai-Hib four-way seedlings (Kantai biology), Baibai-breaking-inactivated polio - Hib Five Miao (Sanofi) issued 706.68 million, 4.2806 million, 4.2559 million, 4.2062 million, respectively, an increase of -35.09 percent, -33.50%, -17.38%, 107.22% yoY The decline of single seedlings is obvious, the substitution trend of joint seedlings is obvious, the decline in the issuance of three-way seedlings is mainly related to the expiration of registration certificates, the decline in the number of four-joint seedlings batch issuance is mainly related to the impact of industry events, and the increase in the number of five-joint seedlings batch issuance is obviously related to the first half of 2018 Since the first Hib-series joint seedlings were listed in 2011, the proportion of the joint seedlings to single seedlings replacement has been more than half HPV vaccine Human papillomavirus (HPV) can cause the proliferation of scaly epithelial epithelial membranes of the human skin, 99.7% of cervical cancer seamounts from HPV infection HPV infection is very common, in most cases the body's immune system in 4 to 6 months to self-removal, but about 0.2% of HPV infection eventually develops cervical cancer More than 200 types of HPV have been detected, of which the highest correlation with cervical cancer infection sis type 16 (51%), 18 (16.2%), type 45 (9%) and type 31 (6%) The HPV vaccine induces the body to produce high-titer viral antibodies that help the immune system remove infections, which in turn reduces the risk of cancer Based on the direct association between HPV infection and cervical cancer and the high incidence of cervical cancer, hpv vaccine has been very noticeable since its inception Global lysing of HPV vaccine, 2 price, 4 price can cover 16, 18 and so on, 9 price 16, 18, 45, 31 and other types, cervical cancer prevention rate as high as 90% Currently, HPV vaccines on the domestic market, including GlaxoSmithKline (GSK) 2 price (Sherry, Mercado 4 (Gadaxiu) and 9-valent HPV vaccine, are imported vaccines The HPV vaccine is well known and the willingness to vaccinate is strong, but demand is not fully released due to the quantity of imported products At present, the quantity of imported products is stable upward, the domestic market in 2019 can reach 10 billion yuan Among domestic manufacturers, more than 10 manufacturers are independently developing HPV vaccine, the fastest progress of Xiamen Wantai Bohai Bio's 2-price HPV vaccine was approved for listing on December 31, 2019, becoming the first domestic domestic cervical cancer vaccine on the market; After the listing of domestic seedlings, it is expected that the market will be divided into self-pricing upgrade market (9 prices) and the government-led price reduction of the base market (2 and 4 prices), the market size will be further enlarged Figure 2 2017-2019 China HPV vaccine batch issuance data source: China Inspection Court from the number of batch issuance, 2019 China's 2-price HPV (GSK), 4-price HPV (Mersadong), 9-price HPV (Mercadong) batch issuance volume is 200.75 million, 484.940,000, 3.3242 million, year-on-year growth -4.95%, 27.61%, 173.35%, 2 prices since the 17-year approval of the listing of the issue gradually stabilized at 2 million, is expected to 2020 4 and 9 prices of HPV issuance will be more than 10 million 13 pneumococcal conjugate vaccine Streptococcus pneumococcus (SP) is the most common pathogen causing pneumonia and may also cause otitis media, sepsis and meningitis Young children and the elderly are the main affected groups 13 pneumococcal polysaccharide combination vaccine (PCV-13) for Streptococcus pneumoniae infection, mainly used in children under 2 years of age and immunocompromised, involving pneumococcal serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F caused by invasive diseases (including pycommas pneumophilia, meningitis, septicaemia and blood About 1.74 million children under the age of 5 suffer from pneumococcal disease in China each year, and 30,000 of them die as a result Wyeth's Prevnar7(Pel7) was launched domestically in 2008 and is the only pneumonia-combined vaccine in the country for quite a long time, targeting seven serotypes In 2015, the import license expired, and the import license stopped supplying the country It wasn't until July 2017 that Pfizer's upgraded version of the 13-price pneumonia vaccine (Pel 13) was officially launched in China to fill the gap in the market Peier 13 tender price per needle 698 yuan, the vaccination procedure three-needle foundation plus one needle to strengthen, a total of 2800 yuan Although the price is more expensive, but because of the early Peier 7 has been cultivated in the market, domestic demand is still strong Assuming 15 million newborns in 2020, the market space could be close to $10 billion, with a 20% vaccination rate At present, pneumonia combined with the lack of vaccine supply, product imports directly affect the market size, market space is expected to be in the domestic products market and solve the capacity problem after the opening Domestic Watson Biology, Minhai Bio, Beijing Kexing, Lanzhou Institute, Zhifei Bio, Kangsino and Chengdu Antekin are independently developing 13-price pneumonia vaccine Table 2 Some domestic enterprises that are independently developing 13-price pneumonia vaccine from the number of batch issues, in 2019 China's 13-price pneumonia combined vaccine (Pfizer) batch issuance volume of 4.755 million, an increase of 23.57 percent year-on-year, production capacity has improved, with the approval of Watson and Kantai products, the market will be further opened Figure 3 Number of pneumococcal combined vaccines issued in the calendar year Source: The Rotavirus Vaccine in the Chinese Hospital sifrot virus vaccine is a vaccine against rotavirus enteritis, mainly for children between 2 months and 3 years of age At present, there is no specific drug treatment for rotavirus infection, the improvement of health conditions can not avoid infection, vaccination is an important and effective means to prevent rotavirus infection At present, rotavirus vaccine has a unit single-price vaccine and pentavalent vaccine, of which the five-valent rotavirus vaccine is a non-oral detoxification vaccine that can prevent five rotaviruses, both subtype coverage, immune success rate and immunization duration are better than single-price vaccines The unit price seedling only one producer in Lanzhou (Rowett), in 2018 Mercadong's five-valent oral rotavirus vaccine to obtain the import drug registration certificate, is expected to rely on better prevention effect and cost-effective advantages gradually to Lanzhou single-price vaccine replacement Domestic research projects, Lanzhou Institute's III price rotavirus gene re-matching vaccine application is listed in the technical review, other enterprises in the research varieties in the early stages In terms of the number of batch issues, china's rotavirus vaccine batch issued 955.73 million in 2019 (unit price of 5.3621 million units, up 4.12% YoY; 5price 4.1952 million, up 429.83 percent year-on-year, from 201 8 years after the market release is obvious), it is expected that the rotavirus vaccine market demand is stable at about 9 million copies, Mershadong Rota Teq (five-price seed) price of about 300 yuan / person, if the rotvirus vaccine market comprehensive coverage, the domestic market space can be close to 3 billion yuan Figure 4 Number of rotavirus vaccine signed for 2017-2019 Source: Vaccines for quadrangle influenza vaccines commonly used in influenza prevention in the Chinese Hospital signed up for influenza are three categories: inactivated vaccines, lysis vaccines and subunit vaccines Among them, the lysate vaccine is the leading in the field of immune effect and side response, and the price is more widely accepted, so it has become the mainstream vaccine of influenza prevention in China The tetravalent influenza virus lysis vaccine contains four influenza virus antigen components of influenza a(H1N1), H3N2, B Yamagata (By), And Bv, which has more Yamagata influenza virus antigen components than the previous trivalent influenza virus lysis vaccine, and its market is expected to benefit from the double benefits of increased vaccination rates and the effects of substitution Figure 5 Distribution of influenza virus vaccine batch issued varieties 2011-2019 Source: Due to the high variability of influenza virus, the current lying influenza vaccine is inefficient compared to other types of vaccines, in addition to its high frequency of vaccination (once a year), resulting in influenza vaccination rate is not other vaccines, the domestic vaccination rate is only about 2% However, from the demand side, with the recent influenza epidemic caused greater social concern, people's awareness of influenza has increased, influenza vaccination rate is expected to be improved in the future At present, more than 80% of the U.S flu vaccine is four prices, due to the late market time, is still in the replacement stage Specifically, there are 14 research companies, of which Hualan Bio was first listed in China in October last year, but there has been a shortage of supply This year, the company stepped up production plans, doubling production capacity last year to 8.36m In addition, Jiangsu Jindik bioproducts approved in October this year after the issuance of 1.35 million units, become a strong complement to the entire four-valent vaccine market, Wuhan is in phase 3 clinical, Zhifei Bio (Anhui Longcoma), Watson Bio, Beijing Kexing, Zhejiang Tianyuan, Liaoning Chengda and Shanghai Institute and other 6 products in the clinical research stage Figure 6 Data on the number of influenza vaccine approvals issued for 2015-2019 Source: China Inspection Court From batch issuance data, the total number of four-price vaccines issued in 2019 reached 971.05 million, an increase of 89.57 percent year-on-year, with market share to 32% On the one hand, the adverse effects of the 2018 long-term problem vaccine event gradually dissipated, the population vaccination rate will increase, the second is that Jiangsu Jindik biological products were approved in October this year, increasing the supply channels of four-price products, and the third is that the substitution effect of the four-price vaccine for the trivalent vaccine is gradually emerging Figure 7 Number of influenza lysate vaccine signed in 2016-2019 Source: China's domestic new vaccine development outlook The global vaccine market has continued to grow in recent years, but at the same time the characteristics of low-frequency vaccine consumption (most vaccinators will not be vaccinated in a single process) have led to intense competition among the same type of products Whether it is the international and domestic markets, the vaccine industry's "micro-innovation" is very rapid, the vaccine product can be short after the market to become a "burst" at the same time, but also face the risk of being easily upgraded by new technology iteration Technology updates include expansion for subtypes, age-level and population-use expansion, greater safety and immunogenicity, and combined vaccines Therefore, from a single product dimension, the vaccine life cycle is limited In 2016-2019, the domestic new vaccine market showed a clear trend of product iteration: triple seedling, four-way seedling, five-way seedling gradually replace Hib single seedling; In the short term, it is expected that by 2020 the domestic 13-price pneumonia vaccine and HPV vaccine are expected to be approved for market, and the new vaccine industry will continue to maintain rapid growth In the long run, the future will usher in the upgrading of changes: MCV4 (tetravalent meningitis vaccine) to the acyW meningitis vaccine, broad-spectrum pneumococcal protein vaccine for 13, 15, 23 price pneumonia vaccine, etc , broad-spectrum influenza vaccine (as long as a few times can produce life-long protection effect, and will not produce resistance to drugs) as a revolutionary change of influenza vaccine.