Economic Observer reporter Zhang Ying On April 11th and 12th, the share price of Wantai Biotech (603392.sh), a leading domestic HPV (human papillomavirus) vaccine company, rose sharply again, with a market value of 97.8 billion yuan, 1,000 yuan away. Billions are just one step away.
On the evening of April 10, Wantai Bio announced that the nine-valent HPV vaccine it developed has completed the unblinding of the main data of the third phase clinical trial. The preliminary analysis results are in line with expectations, and it has begun to write registration and marketing application materials.
Wantai Biotech may become the first company in China and the second company in the world to produce a nine-valent HPV vaccine.
While the share price of Wantai Biotech rose sharply, the share price of Zhifei Biotechnology (300122.sz) continued to fall. The difference in market value between these two companies, which is 5 times different in revenue, is only 170 million yuan. Zhifei Biotech is the exclusive agent in China for the nine-valent HPV vaccine from Merck & Co. (mrk.nyse). From the perspective of the industry, the fierce competition between Wantai Biotech and Zhifei Biotech in China's nine-price HPV vaccine market is inevitable. The
hpv vaccine is the only vaccine in the world that can prevent cancer. The cervical cancer it prevents is the fourth most common cancer that harms women. Currently, there are five HPV vaccines on sale around the world, but only one is the nine-valent HPV vaccine. The nine-valent HPV vaccine covers 9 human papillomavirus subtypes and can prevent 92% of cervical cancer.
Since landing in the capital market in 2020, the "HPV vaccine" label on Wantai Biotech has been eye-catching. The bivalent HPV vaccine developed by the company will be launched on the market in 2020. In recent years, vaccine business revenue has accounted for more than 70% of Wantai Biotech's overall revenue. Among them, the bivalent HPV vaccine is the main contributor.
However, Wantai Biotechnology, which has "bound" the HPV vaccine, is also anxious. On April 8, at the 2023 annual performance meeting held by Wantai Biotech, an investor asked: Merck's nine-valent HPV vaccine age extension has "reduced the commercial value of the two-valent HPV vaccine to zero." You feel the pressure and do you have a plan to deal with it after being beaten for a whole year?
In 2023, Wantai Biotech experienced negative performance growth for the first time since its listing, and its HPV vaccine sales revenue decreased by 4.2 billion yuan year-on-year. Compared with the almost doubling of growth in each of the previous three years, Wantai Biotech in 2023 is even more disappointed. In the past year, Wantai Biotech's share price fell from a high of 120 yuan/share to 40 yuan/share.
Zhong Suisui, the actual controller of Wantai Biotechnology, once divided the world's companies into two categories: one is those that sell "tea eggs", such as Nongfu Spring (09633.hk) and other fast-moving consumer goods companies; the other is those that manufacture "Atomic bomb", such as biomedicine and other high-tech enterprises. Whether a company that builds an "atomic bomb" can do well depends mainly on its level of technological innovation and whether it is in a leading position in the industry.
Now, the domestic bivalent HPV vaccine market has been deeply "involved", and the nine-valent HPV vaccine is expected to become a new growth point for Wantai Biotech. However, unlike the excitement when the nine-price HPV vaccine from Merck & Co. was first launched, in March 2024, the Economic Observer reported that from the eastern megacities to many towns and villages in the west, the nine-price HPV vaccine is no longer hard to find, and the market ceiling is looming. visible. At the same time, Wantai Biotech still has many "chasers", and the nine-valent HPV vaccine from many domestic companies is already in the third phase of clinical trials.
Against the background that there is room for growth in the domestic market, Wantai Biotech’s other path is to go overseas.
overseas market may be a sea of stars. An industry insider familiar with the international vaccine market told the Economic Observer that domestic HPV vaccines are mainly targeting the two major markets of middle-income countries and low-income countries overseas. The potential challenge is that domestically produced HPV vaccines need to face competition from Merck in middle-income countries, and low-income countries need to find ways to enter the Global Alliance for Vaccines and Immunization (Gavi)'s procurement list.
A senior expert on global public health issues said that compared with foreign companies, the advantages of Chinese HPV vaccine companies mainly lie in production capacity and price, while the disadvantage is that some clinical strategies lag behind. For example, the WHO expert group proposed in 2022 that only one shot of HPV vaccine can produce the same immune effect as two or three shots. Merck announced in March 2024 the launch of a clinical trial of a one-shot vaccination regimen for the nine-valent HPV vaccine. If the trial is successful, the price of its nine-valent HPV vaccine may be reduced by two-thirds.
The expert also suggested that Chinese HPV vaccine manufacturers should cooperate with international institutions in clinical trials and publish post-market safety data to enhance the international market's trust in Chinese vaccines. This is also a required course for all Chinese vaccine companies that want to go overseas.
bet on nine-price
In the global market, there are a total of five HPV vaccines on sale, including Merck's quadrivalent and nine-valent vaccines, GlaxoSmithKline's (LSE/NYSE: GSK) bivalent vaccine, and Wantai Biological's Bivalent vaccine, bivalent vaccine from Watson Biotech (300142.sz).
"price" represents the subdivided types of viruses covered by the vaccine. The higher the price, the greater the coverage. Therefore, compared with the bivalent HPV vaccine and the quadrivalent HPV vaccine, the nine-valent HPV vaccine prevents cervical cancer at a higher rate and is more expensive.
The nine-valent HPV vaccine currently on sale around the world is Gardasil 9 from the American company Merck & Co. Jiadaxiu 9 was launched in the United States in 2014 and was approved in China in 2018. It is priced at 1,298 yuan/shot and requires three shots. The
nine-valent HPV vaccine triggered a vaccination craze as soon as it entered China, and stockouts occurred many times. From 2018 to the first half of 2023, the batch release volume of Zhifei Biotech's nine-price HPV vaccine is close to 50 million. Based on 1,298 yuan per shot, it can achieve sales of nearly 65 billion yuan.
The craze for the nine-valent HPV vaccine has squeezed the bivalent HPV vaccine market, especially in August 2022, after the Merck & Co. nine-price HPV vaccine population expanded from 16 to 26 years old to women between 9 and 45 years old.
At present, the government procurement price of Wantai Biological's bivalent HPV vaccine has dropped from 329 yuan/shot to 86 yuan/shot. In 2023, Wantai Biotech's vaccine (mainly HPV vaccine) inventory increased by 91.6% year-on-year; as of the end of 2023, the inventory reached 29.83 million.
The aforementioned expert on global public health issues told the Economic Observer that in the international market, the nine-valent HPV vaccine is a mainstream product. Taking the United States as an example, more than a year after the nine-valent HPV vaccine was launched, the bivalent and quadrivalent HPV vaccines were removed from the government procurement catalog.
A comparable data is that GlaxoSmithKline, the first company to launch a bivalent HPV vaccine, has global sales of bivalent HPV vaccines in the past three years of 130 million pounds, 110 million pounds, and 120 million pounds respectively, while Merck's nine-price vaccine The sales of HPV vaccines in the past three years were US$5.67 billion, US$6.89 billion, and US$8.88 billion respectively.
Four months before Jiadaxiu 9 was launched in China, Wantai Biotech began clinical trials of the nine-valent HPV vaccine. Wantai Biotech's share price has risen many times with the development progress of the nine-valent HPV vaccine.
On August 28, 2020, the Phase III clinical trial of Wantai Biotech's nine-valent HPV vaccine passed the ethical review, and its stock price hit the daily limit that day. In early December 2023, Wantai Biotech stated that the Phase III clinical trial of the nine-valent HPV vaccine had completed its eighth visit. In the following eight trading days, Wantai Biotech's stock price continued to rise, with an increase of more than 60%.
On the evening of April 10, 2024, Wantai Bio announced that its nine-valent HPV vaccine had completed the specimen testing of the 8th visit as planned, completed the unblinding of the trial data and obtained preliminary analysis results of the main data. The main results were in line with expectations. On April 11, Wantai Biotech hit its daily limit.
According to traditional clinical trial requirements, Wantai Biotech needs to complete 12 visits before it can apply for marketing. However, in July 2023, the Drug Evaluation Center of the State Food and Drug Administration issued the "Technical Guidance Principles for Clinical Trials of Human Papillomavirus Vaccine" ( Trial) mentioned that for iterative vaccines (referring to vaccines developed by companies based on the first-generation HPV vaccine research and development platform), clinical trials can be simplified or accelerated to a certain extent.
Wantai Biotech's nine-valent HPV vaccine, as an iterative vaccine, plans to use the 12-month persistent infection endpoint for registration and declaration. The cumulative number of events at the 12-month persistent infection endpoint has been completed at the 8th visit. That is to say, Wantai Biotech only needs to complete the data analysis and trial summary report of these number of events before submitting a registration application to the Food and Drug Administration.
The nine-valent hpv vaccine is no longer hard to find in one shot
Different from the excitement when Merck & Co.'s nine-valent HPV vaccine first came on the market, now, the nine-valent HPV vaccine is no longer hard to get in China.
Although Zhifei Bio believes that the penetration rate of the nine-price HPV vaccine in the Chinese market is still very low, an investigation by the Economic Observer found that in the past, the phenomenon of queuing for two or three years and finding "scalpers" to get the nine-price HPV vaccine at high prices has disappeared. Many companies Community health service centers and township health centers all provide "treatment as soon as you come".
A senior investor who has been paying attention to HPV vaccines for a long time believes that with the help of Zhifei Biological's strong sales network, Merck has pushed the nine-price HPV vaccine to the grassroots in China. The rapid growth stage of the nine-price HPV vaccine market has passed, and the domestic nine-price HPV vaccine has passed. The HPV vaccine may face a red ocean situation when it is launched.
In this "sea", Zhifei Biotechnology has already achieved the widest regional coverage with its industry-recognized sales capabilities. Zhifei Biotech has 3,359 sales staff (2022) and can provide "last mile" services to more than 30,000 primary health service points across the country. The 2023 annual report of Wantai Biotechnology shows that its sales staff are 796, less than a quarter of Zhifei Biotechnology.
In addition, the Chinese companies that have self-developed the nine-valent HPV vaccine include not only Wantai Biotech, but also the nine-valent HPV vaccine from four domestic companies, Watson Biotech, Kangler Guardian (833575.bj), Rico Biotech (02179.hk), and Bowei Biotech. The vaccines are all in Phase III clinical trials. The nine-valent HPV vaccine production capacity planned by each company is large. The planned production capacity of Wantai Biotech is 60 million pieces/year, the planned production capacity of Leisure Guard is 40 million pieces/year, and the initial production capacity of Ruike Biotech can reach 20 million pieces/year. Looking at the entire HPV vaccine market, according to the HPV vaccine batch release data disclosed by various companies, as of the end of 2023, China’s cumulative HPV vaccine vaccination rate (based on women aged 9 to 45 years old) is close to 20%. From a global perspective, the data available for reference is that as of 2020, in countries that have included the HPV vaccine in their immunization plans (paid by the government), their full vaccination rate averages 53%. If calculated at 53%, there are still about 100 million women of school age who have not been vaccinated in China's stock market. However, the actual future growth space and speed also need to consider factors such as immunization policies, vaccine prices, and vaccine hesitancy among Chinese people. A recent study published by Stefano Malvolti, a senior consultant in the
vaccine industry, and others, commissioned by the WHO, shows that the current risk of global HPV vaccine shortages has been significantly reduced, and supply capacity can basically meet demand. It is expected that supply will be available from 2025 to 2030. Quantity is likely to exceed demand.
An executive from a domestic HPV vaccine manufacturer predicted that after a number of domestic nine-price HPV vaccines have been launched, competition in the HPV vaccine market will gradually emerge. Faced with this trend, peers should not consider vicious competition such as price wars. , but should plan ahead for male vaccination groups, catch-up booster shots, and the international market.
There are two ways to go overseas
The ceiling for domestic HPV vaccine growth is looming. In Wantai Biotech's 2023 annual report, the progress of the HPV vaccine overseas was placed at the beginning of the business presentation for the first time.
Wantai Biological's bivalent HPV vaccine is the first domestically produced HPV vaccine to be successfully exported overseas. In October 2021, Wantai Biological Bivalent HPV Vaccine became the fourth HPV vaccine to obtain pre-certification from the WHO after GlaxoSmithKline's bivalent HPV vaccine, Merck's quadrivalent and nine-valent HPV vaccines. The basis for TaiBio's bivalent HPV vaccine to enter the international market.
Since then, Wantai Biotech’s bivalent HPV vaccine has obtained marketing approval in nearly ten overseas countries, including Thailand, Nicaragua, Morocco, and the Democratic Republic of the Congo, and has now been sold in three of them.
According to the above-mentioned industry insiders who know the international vaccine market, domestic HPV vaccines are mainly sold to two types of countries: one is middle-income countries that can bear the cost of vaccine procurement by themselves, such as Thailand and Indonesia; the other is low-income countries (referring to the per capita annual Countries with incomes below US$1,810), such as Congo (DRC), Afghanistan, etc., these countries can receive cost support from gavi in vaccine procurement and immunization program implementation.
Currently, the three countries where Wantai Biotech has successfully achieved sales - Thailand, Nicaragua, and Nepal, are all middle-income countries.
According to the above-mentioned industry insiders, in middle-income countries, Wantai Biotech mainly operates in the public market, that is, government procurement. Each country has to make breakthroughs one by one. It requires patience to introduce the advantages of the product and find local agents to cooperate.At the same time, some countries have requirements for localized production, so Wantai Biotech also needs to find local manufacturers to cooperate with others in order to gain extra points in government project bidding.
He believes that Wantai Biotech currently does not focus on the private market in middle-income countries, mainly because doing so in the private market requires a large number of sales personnel to "circle" around doctors. This is not the choice of Wantai Biotechnology. Companies in the entire industry rarely enter the private market on a large scale. For example, Merck has a very small sales force in middle-income countries, and its sales in these private markets are also very small. In Indonesia, a country with a population of 270 million, less than 50,000 doses of Merck's HPV vaccine are sold in the private market each year.
"The advantage of going through government bidding is that it doesn't require much marketing and promotion expenses. However, the winning bid price in this way is lower and the profit is not as high as in the private market." This industry insider said.
It is not easy to enter low-income countries
Unlike what people think, it is not easy for China's HPV vaccine to enter low-income countries. The general process for purchasing HPV vaccines in low-income countries is: submit purchase requirements to Gavi. After Gavi summarizes the procurement needs of all low-income countries, it will sign a contract with the vaccine manufacturer, and Gavi will bear the purchase costs.
gavi is a Swiss-based vaccine advocacy organization whose founding members include WHO, UNICEF, the World Bank, and the Bill and Melinda Gates Foundation. Its mechanism is similar to global collective procurement, mainly to solve the problem of expensive vaccines from multinational pharmaceutical companies.
"Gavi plays a key role in the vaccine procurement choices of low-income countries." The aforementioned industry insiders who know the international vaccine market said that although vaccine companies can also directly promote to the health authorities of low-income countries, it is recommended that these countries contact Gavi There is a need to purchase vaccines from a certain company, but in many cases, companies may not be able to find communication channels with these countries.
According to the Economic Observer, recently, government workers from low-income countries, which have a population of nearly 100 million, visited Wantai Biotech’s factories. If Wantai Biotech successfully obtains this order, it will be a rare case where Wantai Biotech has won an order from a low-income country through direct promotion. It is not easy for
to enter the main channels of low-income countries (entering Gavi's purchasing list), especially for Chinese vaccine companies that have just entered the international market.
On Gavi’s latest board of directors list, 4 of the 28 directors are from vaccine companies, two of whom are from Merck’s original HPV vaccine team, and the other two are from companies in India and Indonesia. There are no representatives from China among these directors.
gavi conducts a global fundraiser every five years to fund a new round of vaccination programmes. In the ranking of donations in 2020, China ranked 18th in the world. The top two are the United States and the United Kingdom, followed by Germany and the Gates Foundation.
At present, gavi has launched the fundraising work for the 2026-2030 vaccine plan. The above-mentioned industry insiders predict that Gavi will launch the bidding for HPV vaccines from 2026 to 2030 in 2024, and complete the signing of contracts with suppliers in 2025. "2024 is a very critical year, and Gavi has already launched fundraising activities."
