Where does the contradiction between supply and demand come from?
The domestic potential stock market is 194.8 billion yuan, which will take 10 to 15 years to digest
According to the "Chinese Expert Consensus on the Clinical Application of Human Papillomavirus Vaccines", human papillomavirus (HPV) is the most common pathogen of reproductive system diseases, which can cause epithelial hyperplasia of human skin and mucous membranes, and is mainly transmitted through sexual life or close contact.
More than 80% of women have at least one HPV infection in their lifetime, more than 90% of HPV infections can be cleared naturally within 2 years, and less than 1% of patients develop cervical precancerous lesions and cervical cancer.
The HPV vaccine, which prevents human papillomavirus infection, is currently the only vaccine that has been shown to prevent cancer.
It has been 6 years since the HPV vaccine entered the domestic market, and the batch issuance has shown an increasing trend. Especially with the addition of local enterprises, the HPV vaccine has shown a rapid growth trend, with a compound growth rate of nearly 120%.
According to the forecast of the research report, the potential stock market of HPV vaccine in China is 194.8 billion yuan.
HPV vaccine has been on the market in China for 6 years, and local companies have risen
Data from the World Health Organization's Global Strategy to Accelerate Cervical Cancer Elimination show that more than 100 different types of HPV are known and at least 14 are known to be carcinogenic.
Of these, the two highest-risk strains, HPV-16 and HPV-18, are responsible for approximately 70% to 80% of cervical cancer cases.
Up to now, there are 4 companies in the world that can produce HPV vaccines.
In 2006, Merck developed the world's first HPV vaccine "Jia Daxiu", which was listed in the United States through priority approval.
Subsequently, GlaxoSmithKline also produced the bivalent HPV vaccine "Huiyankang".
Since then, the HPV vaccine has been launched in more than 100 countries and regions around the world, and it has been widely vaccinated in women.
Based on the good clinical protective effect and safety data of HPV vaccine, the World Health Organization has issued recommendations to encourage the use of HPV vaccine in suitable populations to reduce the incidence of cervical cancer.
Ten years later, the HPV vaccine came to China.
In July 2016, the former State Food and Drug Administration approved the application for import registration of GlaxoSmithKline's (GSK) prophylactic biological product - human papillomavirus adsorbed vaccine.
Among them, clinical research occupies a considerable part of the time.
The data disclosed at the time of GSK's approval indicated that before its vaccine product was approved by the State Food and Drug Administration, it had conducted clinical studies in China for six years, collecting data on more than 6,000 subjects (including the vaccination group and the control group). Group).
There are also data showing that before GSK's HPV vaccine was approved for marketing in the United States, it had begun to recruit clinical trial volunteers in China to prepare for entering the Chinese market.
In May 2017, Merck's quadrivalent HPV vaccine was approved for marketing in China, becoming the second imported HPV vaccine to enter my country after GSK bivalent HPV vaccine.
On April 28, 2018, Merck's nine-valent HPV vaccine was also approved to enter the domestic market.
At the same time, the bivalent HPV vaccines of two local companies, Watson Bio and Wantai Bio, broke the market dominance of foreign companies. day approved.
In March 2022, the State Food and Drug Administration issued the drug approval document of Yuxi Zerun bivalent human papillomavirus vaccine (Pichia pastoris), a wholly-owned subsidiary of Watson Biological Holdings subsidiary Shanghai Zerun, becoming the second domestically produced product. Bivalent HPV vaccine.
Policies are frequently introduced at the national and local levels to promote the popularization of HPV vaccines.
From 2017 to 2020, the HPV vaccine showed a rapid growth trend, with a compound growth rate of nearly 120%.
In 2019, a total of 10.8754 million HPV vaccines were issued in batches in my country, including 3.3242 million batches of Merck's nine-valent HPV vaccine, 5.5437 million batches of quadrivalent HPV vaccine, and 2.0075 million batches of GSK's bivalent HPV vaccine.
According to Zhongtai Securities’ calculation based on the winning bid price of the three categories, the total of the three is close to 10 billion yuan, making it the first vaccine category of 10 billion yuan.
In 2020, a total of 15.43 million HPV vaccines were approved and issued in my country, including 690,000 GSK bivalent HPV vaccine, 7.22 million Merck quadrivalent HPV vaccine, 5.07 million nine-valent HPV vaccine, and 2.46 million Xiamen Wantai bivalent HPV vaccine branch.
According to the winning bid price of 3 categories, the total batch issuance amount exceeds 13.5 billion yuan.
Starting from April 2021, the China National Institute for Food and Drug Control (“China Institute for Inspection and Quarantine”) will no longer disclose the specific number of vaccine batches (bottles) issued, only the batches issued by the batch.
In the whole year of 2021, a total of 253 batches of HPV vaccines were issued, a year-on-year increase of 143%.
Among them, Wantai Bio’s bivalent HPV vaccine was issued the most times, reaching 163 batches; GSK bivalent HPV vaccine was issued in 5 batches, down 71% year-on-year; MSD’s quadrivalent and nine-valent HPV vaccines represented by Zhifei Bio were 38 batches and 42 batches, with year-on-year growth rates of 23% and 75% respectively.
Cheaper prices and wider vaccination age groups allowed Wantai Bio's bivalent HPV vaccine to quickly seize the market after it was launched.
According to the research report of Xiangcai Securities, since the launch of the first domestic bivalent HPV vaccine, the substitution effect on imported bivalent HPV vaccine has been obvious.
According to the data disclosed by Wantai Bio in June this year, its bivalent HPV vaccine is sold to CDCs across the country in a direct sales model. Its business channels have effectively covered more than 2,500 district and county CDCs across the country, with more than 18,000 vaccination sites under its jurisdiction. , and will be extended to more vaccination sites in the future.
In the first half of this year, a total of 150 batches of bivalent HPV vaccines were issued, a year-on-year increase of 206%, mainly by Wantai Bio and Watson Bio.
Wantai Bio is still the most, with a total of 142 batches issued in the first half of this year; Watson Bio has issued 6 batches.
In the first half of this year, Zhifei Bio’s quadrivalent HPV vaccine was issued in 29 batches, a year-on-year increase of 107%; the 9-valent HPV vaccine was issued in 44 batches, a year-on-year increase of 450%, exceeding the full year of 2021.
Huaan Securities Research Report pointed out that the rebound in vaccination demand and the increase in supply have jointly promoted the unprecedented high growth rate of HPV vaccine.
The domestic storage market is huge, and enterprises continue to expand production
Faced with the huge market for HPV vaccines, various companies continue to expand production.
In July 2021, Wantai Bio launched a 20 million/year vial-packed vaccine based on the pre-filled syringe packaging with a bivalent HPV vaccine production capacity of 10 million/year, and the annual production capacity has now reached 30 million.
In many exchanges with investors this year, Wantai Bio mentioned that the production and sales of bivalent HPV vaccine are linked, and due to the shortage of market supply, full production is underway.
Through optimizing processes and lean management, it is expected to increase production capacity by 10%-20%.
However, the scale-up of the process is affected by the expression amount of the stock solution expression system, and it takes a certain time.
The strategy adopted by Wantai Bio is to give priority to ensuring the speed of listing, to seize the window period while taking into account reasonable production capacity.
"Wantai's market strategy is to sink the self-funded market into third- and fourth-tier cities. These are markets that multinational companies are not involved in. However, Wantai did not expect when it first built production capacity, and the demand in third- and fourth-tier cities will also be the same. In addition to the rapid advancement of the HPV vaccine immunization program, the original design production capacity may not keep up with the rapid development needs of the market." An expert in the vaccine industry told the Beijing News reporter that even if the design production capacity and process of the company are optimized, it can be improved. Capacity is still limited unless major changes are made to the process or new production lines are built, which all require re-doing of process pharmacy, clinical validation, evaluation and approval.
At the same time, Wantai Bio also mentioned that after the nine-valent HPV vaccine is put on the market, if the economic capacity allows, everyone will be more inclined to receive the nine-valent HPV vaccine. In the future, production capacity and promotion will also focus on the nine-valent HPV vaccine. The HPV vaccine is now being prepared for conversion. It needs to open up the original solution process, conduct clinical trial verification, and perform the approval process. It is expected that when the nine-valent HPV vaccine is launched, the production capacity of the bivalent HPV vaccine can be converted to the nine-valent HPV vaccine.
Watson Bio's HPV vaccine production workshop in Yuxi, Yunnan has also been completed, and obtained a drug production license issued by the Yunnan Provincial Food and Drug Administration in 2018. The annual output of vaccines is 30 million doses, which is directly the same as Wantai Bio's existing production capacity.
"The government immunization program market and the Global Alliance for Vaccines and Immunization (Gavi) market will be our focus." Li Wei, general manager of Yuxi Zerun, a wholly-owned subsidiary of Watson Bio, said that they attach great importance to government immunization programs for the 9-14 age group In addition to winning the bid for Nanjing HPV vaccine procurement, the project is also promoting the products to enter other local government immunization planning projects.
At the same time, it also cooperates with the Women's Federation, and will promote the health education of girls in the future.
In addition, supplying the Gavi market and entering the international market will also be the focus of Watson Bio.
"Supplying the Gavi market is a corporate social responsibility. Once it passes the World Health Organization pre-qualification (PQ), it will help Watson to establish an international image and open up overseas markets." Li Wei said that Watson will try its best to do a good job in the domestic market and prepare for Sufficient goods, to ensure that the domestic market supply will not be affected after passing the PQ, especially to fully protect the government's immunization program.
Watson's bivalent HPV vaccine is in the early stage of market promotion. It is expected that the production volume will increase rapidly from September this year, and the market will be established through the government's immunization planning project as soon as possible. Expansion plans are also being planned.
Li Wei said that the nine-valent HPV vaccine is in the clinical stage and it may take three or four years.
The nine-valent HPV vaccine is in short supply, and because of its high unit price, it is mainly sold in the self-funded market.
What about the supply strategies of the two foreign companies, GSK and Merck?
Neither party responded by press time.
However, in an interview with the Beijing News in January this year, Merck said that in the face of the domestic market demand that is far from being met, it plans to expand the supply of HPV vaccines.
At that time, Merck said that due to the impact of the new crown epidemic, the global confidence in vaccines has continued to increase, which has increased the demand for HPV vaccines in various countries.
The supply expansion trend can be seen from the purchase amount of its agents.
Merck and Zhifei Biotechnology have cooperated in marketing since April 2011, and the latter is responsible for the import, promotion and sales of Merck's vaccine products in mainland China.
In December 2020, Zhifei Bio announced that on the basis of previous cooperation, it signed an agreement with Merck again to determine the basic purchase amount of five vaccine products that have obtained marketing licenses in mainland China in the next two and a half years, totaling more than 30 billion.
The two parties have agreed on the agreed products and the expected basic purchase amount. From June 2021 to June 2023, the basic purchase amount of HPV vaccines (tetravalent and nine-valent) will be 10.289 billion yuan (2021) and 11.557 billion yuan (2022), respectively. ), 6.26 billion yuan (January-June 2023); the two parties also agreed that Merck can increase the supply and basic purchase amount according to the actual situation.
Among them, the HPV vaccine can be raised to 12.040 billion yuan in 2021, 13.596 billion yuan in 2022, and 8.943 billion yuan in 2023.
There are only four production enterprises, and the global supply and demand "balance" is out of balance
The introduction of HPV vaccine in China is relatively short, nearly ten years later than that in Europe and the United States. Although the number of batches has increased rapidly, the penetration rate is still low, and the domestic demand for HPV vaccination is far from being met.
According to the "2018-2020 Estimated Vaccination Rate of Human Papillomavirus in Chinese Women Aged 9-45" jointly published by Song Yifan and other 9 people from the Immunization Planning Center of the Chinese Center for Disease Control and Prevention, it is estimated that in 2018-2020, China's 9-45-year-old A total of 21.5974 million doses of HPV vaccine were vaccinated by school-age women, and the cumulative estimated vaccination rate was only 2.24%. Even the highest in Beijing, Shanghai, and Zhejiang provinces only reached 8.28%, 7.37%, and 4.68%, respectively.
The updated data is the penetration rate of about 6% mentioned by Wantai Bio when it communicated with investors in May this year.
This also means that there is still a large vaccination market for HPV vaccines in China.
The Sinolink Securities Research Report estimates that the potential stock market for HPV vaccines in China is 194.8 billion yuan.
Wantai Bio mentioned that from the perspective of domestic market capacity, according to the sixth census data released by the National Bureau of Statistics, the current domestic HPV vaccine stock market is about 380 million people (9-45 years old), and there will be new ones every year. market.
Some insiders in the vaccine industry mentioned that although the four vaccine manufacturers are increasing their production capacity, according to the upper limit of the existing production capacity, the domestic memory market alone is expected to take 10 to 15 years to "digest".
Globally, only 4 companies can produce HPV vaccines, and the "balance" of supply and demand has long been out of balance.
It is less than a decade away from the World Health Organization's target of 90% HPV vaccine coverage by 2030.
"If the entire age group from 9 to 45 years old pursues the HPV vaccine at the same time, the pressure of the contradiction between supply and demand can be imagined, and the expansion of production capacity cannot be realized in the short term, and there will be a problem of market distribution of products." Bill & Melinda Gates Foundation Du Heng, senior project officer of the Association, pointed out that for multinational vaccine companies, the immunization planning market in high-income countries such as the United States and the United Kingdom has a large purchase volume and high pricing, which is one of the important markets for companies.
Although China has not yet included the HVP vaccine into its national immunization plan, the HPV vaccine is still in the self-funded market, but because of the large demand, multinational companies often give priority to ensuring the supply.
In addition, there is another important market, that is the Gavi (Global Alliance for Vaccines and Immunization) market, because Gavi concentrates the needs of 73 low- and middle-income countries and forms a scale effect. It is a crucial global health public goods market and is also a Chinese vaccine. An important target market for the internationalization of enterprises.
In 2011, Gavi launched the HPV vaccine funding plan. According to the research report of Guosen Securities, from 2010 to 2016, the global HPV vaccine market size was about 230 million doses, of which 5.5 million doses were supported by Gavi countries; 40 million school-age girls will be vaccinated by the end of the year, but due to the increasing global demand for HPV vaccines and production capacity bottlenecks, only about 14 million people will actually be vaccinated.
On the evening of June 4, 2020, Beijing time, at the Gavi fundraising meeting, Merck, GSK, Wantai Bio, Watson Bio, etc. pledged to increase and give priority to providing HPV vaccines to Gavi-supported countries. In the next five years, Gavi will provide its services The range has increased from an initial plan of 50 million school-age girls to 84 million.
Gavi predicts that global HPV vaccine demand will increase to 120 million doses per year in 2030, of which about half is Gavi demand.
At this fundraising meeting, Li Yunchun, chairman of Watson Bio, also promised that after obtaining WHO pre-qualification (PQ), Watson Bio will allocate more than half of the bivalent HPV vaccine production capacity in the future and supply it at an affordable price Gavi Markets fully supports the Gavi 5.0 strategic plan that will benefit 84 million women aged 9 to 14 worldwide.
In October 2021, Wantai Bio's bivalent HPV vaccine was pre-certified by the World Health Organization.
Some investors have asked Wantai Bio, what is the significance of applying for WHO pre-certification in the context of the current shortage of supply in the domestic market?
In this regard, Wantai Bio said that the company's positioning of its products is to enter the international market. Some countries need to pass WHO pre-certification before they can register. Therefore, passing WHO pre-certification is also a product technology and quality that meet international standards. Best proof.
At present, Wantai Bio has deployed overseas markets, mainly targeting Asian and African countries, most of which are in the registration stage.
In May of this year, Wantai Bio's bivalent HPV vaccine was approved for marketing in Morocco, which is the first time that the vaccine has been approved for overseas marketing.
However, Wantai Bio said that there is currently a large domestic demand for HPV vaccines, and the production capacity will give priority to ensuring the domestic market demand and then gradually export.
Watson Bio has also submitted WHO pre-certification. Its production workshop in Yuxi, Yunnan not only complies with domestic GMP standards, but is also designed and constructed according to WHO pre-certification standards under the technical guidance provided by international vaccine experts. The bivalent HPV vaccine will be pre-certified by the World Health Organization more quickly and will be supplied to the global public goods market. This step will also allow Watson Bio's bivalent HPV vaccine to enter the international market with wider demand.
【Disambiguation】
What does "price" mean?
The HPV vaccine mainly induces the humoral immune response of the body, and the neutralizing antibodies produced can bind to the virus antigen when HPV enters the body, thereby preventing HPV infection.
Block the occurrence and development of cervical precancerous lesions by preventing primary HPV infection and reducing persistent HPV infection.
The "price" in the HPV vaccine represents the types of viruses that the vaccine can prevent. The higher the number, the more types of viruses that can be prevented.
What is the best age for vaccination?
On November 17, 2020, the World Health Organization released the "Global Strategy to Accelerate the Elimination of Cervical Cancer". For the first time, 194 countries pledged to eliminate cervical cancer, and proposed three key measures to achieve this goal: vaccination, screening and treatment .
According to the recommendations of research and domestic and foreign guidelines, the best population for HPV vaccination is girls aged 9-14, and women aged 15-45 are also necessary to be vaccinated. The earlier the vaccination, the better the effect.
Is HPV positive cancer?
HPV infection is not uncommon, and 80% of women will be infected with HPV during their lifetime.
However, having HPV does not necessarily mean that cervical cancer will occur.
HPV positive only indicates HPV infection. At this time, there is still a long distance from the real disease. More than 80% of HPV infections will be cleared naturally within 8 months, and only a few persistent high-risk HPV infections may cause cancer.