On the morning of April 14, some media reported that the World Health Organization (WHO) recently released news on its official website that the organization held a meeting of the Strategic Expert Group on Immunization (SAGE) from April 4 to 7.
Evidence for single dose of human papillomavirus (HPV) vaccination was considered and concluded that a single dose of HPV vaccination regimen was effective in preventing cervical cancer caused by persistent HPV infection and was comparable to the effectiveness of two or three doses.
Affected by the above news, HPV vaccine-related concept stocks fell sharply, The intraday stock price of Zhifei Bio (300122) flashed and collapsed, and Wantai Bio (603392) fell to a halt during the intraday.
Compared with companies that have been listed, the decline of HPV vaccine manufacturers in research is less obvious, and Watson Bio (300142), which has just been approved to be listed for bivalent HPV vaccines, once fell to 7% in the early market, and the decline has narrowed to 3% as of the close; Hong Kong stock Ruike Bio (02179. HK) also turned red at one point.
It is reported that the SAGE meeting minutes mentioned that for people with weakened immune systems, three doses will be considered the best. In addition, minor changes to vaccinations require a series of clinical, data support, and registration changes.
Some brokers believe that the above content is a protective recommendation for women in some poor countries with extremely low vaccine coverage, and has no impact on the standard vaccination procedure of three-shot vaccines on the mainland. Some insiders also told the Securities Times E company reporter that the short-term impact is limited, after all, the HPV vaccine gap in the mainland is still very large. At the same time, relevant leading companies also told reporters that their influence was limited.
Emergency response from the relevant company
This morning, Zhifei Bio originally opened slightly higher by about 1 percentage point, and the trend was stable before 10:19, and the stock price remained above 130 yuan / share. However, with the spread of the above news, the stock price of Zhifei Bio quickly dived, and the stock price fell to about 110 yuan / share, down more than 18%, and the stock price narrowed in the afternoon.
SAGE has reviewed new evidence on the efficacy of a single-dose HPV vaccine. Based on all available evidence, SAGE recommends that countries can choose between a single or two-dose vaccination schedule when developing HPV vaccination programmes for girls aged 9 to 14 years, as a single dose and two doses have the same and effective protective effect. In addition, young women aged 15 to 20 years can also be given a single or two dose vaccination schedule, while women over 21 years of age should be given a two-dose vaccination schedule with an interval of 6 months.
The WHO SAGE conference mentioned that for people with weakened immune systems, more evidence is needed to show that reducing the number of vaccination doses can still have a protective effect on them. Until further evidence is available, priority should be given to immunocompromised people aged 9 years and older and given at least two doses of the vaccine, but if feasible, three doses of the vaccine will be considered the best option.
In response to the above reports, Zhifei Biological related people told the Securities Times e company reporter that in order to expand the coverage of hpvic vaccination in women around the world, the WHO began to promote a dose of HPV vaccine as early as 2018, and this is not the first time to propose. The immunization program of the vaccine requires a large amount of clinical trial data as a support, the State Food and Drug Administration will approve the listing, and the company is also communicating with Merck and relevant departments in a timely manner to understand the situation.
Wantai Bio issued a note announcement that as of now, the company has only obtained a domestic vaccine registration license, and has not yet obtained a foreign national vaccine registration license. At present, the bivalent HPV vaccine approved by Wantai Bio in China is 3 doses (women aged 9 to 14 years can take 2 doses). Under the current national drug regulatory policy, if the secondary change of vaccination is carried out, a series of clinical, data support and registration change procedures need to be performed, which takes a certain amount of time, and there is no significant impact on the company's operating performance in the short term.
In addition, Wantai Bio also reminded the risk that before the national policy change, the company will continue to sell according to the current approved doses, but in the future, it is not excluded that WHO and the domestic government will actively promote the 1 or 2 doses of immunization procedures. If existing manufacturers and new entrants are approved for registration through clinical trials and registration changes, etc., to promote the 1-dose or 2-dose immunization procedure in China or abroad, it will have a greater impact on the market supply and immunization of cervical cancer vaccines as a whole.
How much impact does the brokerage interpretation have
How big is the impact in practice? Many voices believe that the impact on the industrial chain in the short term is not large.
Analysts at BOC Pharmaceutical believe that the "HPV one-shot method" does not affect demand, but may bring more incremental opportunities. The analyst believes that the starting point of the discussion at this meeting is the slow progress of HPV vaccination globally and the overall low vaccination rate (especially in poor countries). DR Cravioto, chair of SAGE, said SAGE had made the recommendation to be able to get more women vaccinated.
The analyst explained that the starting point of SAGE's recommendation for HPV vaccine at this meeting is to allocate limited capacity to more women, so it does not affect the demand for HPV vaccine, but only recommends the allocation. The HPV vaccine remains one of the most scarce vaccines in the world. From another point of view, the WHO attaches great importance to HPV vaccines, which further illustrates the necessity and scarcity of HPV vaccines.
In addition, the main target of this recommendation is poor countries, with the aim of rapidly increasing HPV vaccination rates in poor countries. For China, Europe and the United States, as well as other developed countries, the marketing of HPV vaccines must be verified by rigorous clinical trials, and the adjustment of the listed vaccination procedures needs to go through a rigorous demonstration and experimental process, and it is almost impossible to make adjustments in the short term.
In addition, Soochow Pharmaceutical commented that antibodies can also be detected in women who receive one injection of HPV vaccine, and the rate of viral infection is lower than that of unimmunized women, but the long-term protection efficiency has not been verified by phase III clinical trials, and the antibody titer in one injection of women is significantly lower than that of three injections.
The chief doctor of a top three hospital told reporters that he also believes that the above news has a limited impact on actual demand, on the one hand, the domestic HPV vaccine is in short supply, even if the age of women only vaccinate one injection of HPV, the current supply is insufficient; on the other hand, the above news does not deny that the effect of three injections is stronger than one injection, from this point of view, people with conditions will still choose three injections, just like "Everyone knows that the bivalent vaccine has been able to resist more than 80% of the HPV virus, But everyone will still prefer to choose the same as the nine-price."
For the average woman, three-dose vaccination is always the most protective and well-documented modality. Soochow Brokerage believes that the latest news is the WHO's public welfare recommendation, which is a protective recommendation for women in some poor and extremely low-vaccine countries, and has no impact on the standard vaccination procedure of our country's three-shot vaccine.
In addition, doctors in related fields told the Securities Times E company reporter that this guidance practice will not be of great significance, playing HPV is not a strong will to implement, but depends on personal will, conditional vaccination personnel will definitely choose high-standard products. It's like the bivalent HPV vaccine is already able to protect against more than 80% of the HPV virus, but most people with conditions are still willing to choose the nine-valent vaccine.
Merck: Vaccination regimens should be rigorously scientifically demonstrated
In response to the above situation, securities times · e company reporters learned from Merck China that the current four-valent and nine-valent HPV vaccine immunization program listed in China is three doses, and the protocol is based on the approved indications of clinical research data in China.
Merck China said that the vaccination program of the vaccine should be based on strict scientific arguments, Merck's quadrivalent and nine-valent HPV vaccines have accumulated a large number of clinical trials and real-world data in terms of protective efficacy, protective effect, safety and durability of protection, and were approved for listing by the State Drug Administration of China (formerly the State Food and Drug Administration) in 2017 and 2018.
Merck China further noted that the efficacy and safety of two doses, a single dose, or other immunization procedures not approved by regulatory agencies for Chinese populations have yet to be further confirmed. Merck China recommends that healthcare professionals and consumers follow regulatory-approved HPV vaccine instructions.
Merck said the company is committed to protecting the health of Chinese women through HPV vaccines and helping Chinese women of the right age reduce the risk of HPV-related cervical cancer and other related diseases. Currently, Merck's quadrivalent and nine-valent HPV vaccines have been approved for use in adolescents in some markets outside of China.
In recent years, Merck has invested more than $1 billion to increase the capacity of existing HPV vaccine production facilities and build new ones. Merck's global supply of HPV vaccines nearly doubled from 2017 to 2020, and it is expected that Merck's global supply of HPV vaccines will double again from 2020 to 2023.
With the increase in global production capacity, Merck's supply of HPV vaccines to China has also increased year by year. In the first quarter of 2022, merck's quadrivalent HPV vaccine shipments increased by nearly 70% year-on-year, and the number of approvals for nine-valent HPV vaccines increased by nearly 280% year-on-year. Merck said it will continue to increase the supply to the Chinese market to meet the growing demand for HPV vaccines from more women and contribute to the development of Public Health in China.
There is a large gap in the supply of HPV vaccines
According to the World Health Organization, cervical cancer is one of the most common gynecological malignancies and the second most common cancer among women aged 15 to 44 years worldwide. HPV has a direct correlation with cervical cancer, the HPV vaccine is the world's first vaccine to be used to prevent tumors, and humans are the first to try to eliminate a cancer through vaccines. At present, there are three main types of HPV vaccines commercialized in the world, namely HPV divalent vaccine, HPV quadrivalent vaccine and HPV helivalent vaccine.
At present, the products that have been listed in the domestic market are mainly nine-valent and quadrivalent vaccines imported from Merck, and there are also some domestic tetravalent and bivalent vaccines, and the current recommended number of vaccination injections is 3 doses. At present, the HPV vaccine market in mainland China is mainly divided by four vaccines, including Citronine (bivalent) of Wantai Biotech, Cervarix of GlaxoSmithKline (bivalent) of the United Kingdom, Gardasil (quadrivalent) and Gardasil9 (nine-valent) of Merck in the United States.
It is worth noting that the quadrivalent HPV vaccine, which is exclusively represented by Zhifei Bio, was officially put on the market in November 2017, and the initial sales of the product were hot, and there was a phenomenon of "grabbing seedlings". Subsequently, the nine-valent HPV vaccine has been in a state of "one injection is difficult to find" after the listing, and all parts of the country need to make an appointment to administer, and the current two-valent and four-valent HPV vaccines are also in short supply.
There is still a big gap in the current supply of HPV vaccines in the mainland. According to Frost & Sullivan, HPV vaccination rates on the continent are low overall (less than 1%); if you take into account the expected increase in HPV vaccination rates, it is expected that 234 million women aged 9 to 45 years will remain unvaccinated against HPV by 2050.
In the face of a market of short supply, many domestic companies have joined the ranks of developing HPV vaccines.
On the evening of March 15, Chengda Bio issued an announcement that the 15-valent HPV vaccine developed in cooperation with Connaught Guardian received the "Notice of Approval of Drug Clinical Trials" approved by the State Drug Administration, which approved the fifteen-valent HPV vaccine to carry out clinical trials; Watson Bio announced on the evening of March 28 that Zerun Biologics, an indirect holding subsidiary of the company, recently received the "Drug Registration Certificate" of the bivalent human papillomavirus vaccine (Bichi Yeast) approved by the State Food and Drug Administration.
According to the research report of Huaan Securities, in the field of nine-valent vaccines, in addition to Connaught Guardian and Ruike Biologics, Bowei Biologics and Wantai Biologics have also entered the phase III clinical stage. In the field of quadrivalent vaccines, there are 3 clinical products, and the fastest progress at present is Bowei Biology and China Biology, which have entered the Phase III stage. In the field of bivalent vaccines, Watson Bio has made the fastest progress and has entered the marketing application stage.
(Editor-in-charge: Peng Bo Courtesy photo: Wu Zhi)
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