Securities Times reporter Chen Lixiang and Tang Qiang

  On the morning of April 14, some media reported that the World Health Organization (WHO) recently announced on its official website that the organization held a meeting of the Strategic Expert Group on Immunization (SAGE) from April 4 to 7.

A review of the evidence for single-dose human papillomavirus (HPV) vaccination concluded that a single-dose HPV vaccination regimen was effective in preventing cervical cancer caused by persistent HPV infection and was comparable to a two- or three-dose regimen. The effect is comparable.

  Affected by the above news, HPV vaccine-related concept stocks plummeted, Zhifei Bio (300122) crashed intraday, and Wantai Bio (603392) fell by the intraday limit.

Compared with companies that have already listed, the decline of HPV vaccine manufacturers in research and development is less obvious. Watson Bio (300142), which has just been approved for the listing of bivalent HPV vaccine, once fell to 7% in early trading, and the decline has narrowed to 3% as of the close. %; Hong Kong stock Ruike Bio (02179.HK), which is expected to launch the first domestically produced nine-valent vaccine, also turned red for a while.

  It is reported that the SAGE meeting minutes mentioned that for the immunocompromised population, three doses would be considered optimal.

In addition, a series of clinical, data support and registration change procedures need to be performed to make changes in vaccination doses.

Some brokerages 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 my country's three-injection vaccine.

Some people in the industry also told the reporter of Securities Times · e company that the short-term impact is limited, after all, there is still a large gap in my country's HPV vaccine.

At the same time, relevant leading companies also expressed limited influence on reporters.

Related company emergency response

  In early trading on the 14th, Zhifei Bio opened slightly higher by about 1 percentage point, and the trend was stable before 10:19, and the stock price remained above 130 yuan per share.

However, with the spread of the above-mentioned news, the share price of Zhifei Biology plunged rapidly, dropping to about 110 yuan per share, a drop of more than 18%, and it narrowed in the afternoon.

  It is reported that SAGE reviewed new evidence on the efficacy of single-dose HPV vaccine.

Based on all available evidence, SAGE recommends that countries choose a single-dose schedule or a two-dose schedule when planning HPV vaccination for girls aged 9 to 14 years, as single-dose vaccination and two-dose vaccination have the same Efficient protection effect.

In addition, young women between the ages of 15 and 20 can also use a single-dose or two-dose schedule, while women over the age of 21 should use a two-dose schedule, with the two doses being given 6 months apart.

  The WHO SAGE meeting mentioned that for immunocompromised people, more evidence is needed to prove that reducing the number of vaccine 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 with at least two doses of the vaccine, but three doses would be considered optimal if feasible.

  In response to the above reports, a relevant person from Zhifei Bio told a reporter from Securities Times e Company that in order to expand the coverage of HPV vaccination among women worldwide, the WHO started to promote one-shot HPV vaccination as early as 2018, and this is not the first time that it has been proposed.

The immunization program of the vaccine requires a large amount of clinical trial data as support, and 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 has issued an explanatory announcement. Up to now, the company has only obtained the domestic vaccine registration license, and has not yet obtained the foreign country vaccine registration license.

At present, the bivalent HPV vaccine approved by Wantai Bio in China is 3 doses (2 doses for women aged 9-14).

Under the current national drug administration policy, such as changes in vaccination doses, a series of clinical, data support and registration change procedures need to be performed, which will take a certain amount of time and will not have a significant impact on the company's operating performance in the short term.

  In addition, Wantai Bio also reminded related risks. Before the national policy changes, the company will continue to sell according to the currently approved doses, but in the future, it is not ruled out that the WHO and the domestic government will actively promote 1-dose or 2-dose vaccination Immunization program.

If existing manufacturers and new entrants are approved for registration through clinical trials and registration changes, and promote 1-dose or 2-dose immunization procedures at home or abroad, it will have a greater impact on the market supply and immunization of the entire cervical cancer vaccine. big impact.

Brokerage Interpretation Impact

  How big is the impact actually?

Many voices believe that there will be little impact on the industry chain in the short term.

  Analysts from Bank of China Pharmaceutical believe that the "HPV one-shot method" will 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 global HPV vaccination and the overall low coverage (especially in poor countries).

Dr. Cravioto, chairman of SAGE, said that SAGE made this recommendation to allow more women to be vaccinated.

  The above-mentioned analysts explained that the starting point of SAGE's recommendations for HPV vaccines at this meeting is to allocate limited production capacity to more women, so it does not affect the demand for HPV vaccines, but only recommends allocation.

The HPV vaccine remains one of the most in-demand vaccines in the world.

From another perspective, WHO attaches great importance to HPV vaccine, which further illustrates the necessity and scarcity of HPV vaccine.

  In addition, the main target of this proposal is poor countries, and the purpose is to rapidly increase HPV vaccination rates in poor countries.

For China, Europe and the United States and other developed countries, the marketing and use of HPV vaccines must be verified by strict clinical experiments, and the adjustment of the vaccination program of the marketed vaccines requires a rigorous demonstration and experimental process, and it is almost impossible to make adjustments in a short period of time.

  In addition, Soochow Medicine commented that antibodies can also be detected in women who received a dose of HPV vaccine, and the virus infection rate was lower than that of women who were not vaccinated. However, the long-term protection efficiency has not been verified by phase III clinical trials. The titer was significantly lower than that of three injections.

  The chief doctor of a tertiary hospital told reporters that he also believes that the above news has limited impact on actual demand. On the one hand, the domestic HPV vaccine is in short supply. Even if every woman of school age is only vaccinated with 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 that of one injection. From this point of view, people who have the conditions will still choose three injections, just like "everyone knows that the bivalent vaccine can protect against more than 80% of HPV viruses. But everyone will still tend to prefer the same price as nine."

  For the average woman, three doses of vaccination are always the most effective and well-documented form of protection.

Soochow Securities believes that the latest news is a recommendation of a public welfare nature by the WHO. It is a protective recommendation for women in some poor countries with extremely low vaccine coverage, and has no impact on my country's standard vaccination procedures for the three-shot vaccine.

  In addition, some doctors in related fields told the reporter of Securities Times · e company that this guidance will not be of great practical significance. HPV vaccination is not mandatory, but depends on personal wishes. Conditional vaccinators must choose high-standard products.

This is like, the bivalent HPV vaccine has been able to protect more than 80% of HPV viruses, but most people who have the conditions are still willing to choose the nine-valent vaccine.

Merck: Vaccination Program

Strict scientific justification

  In response to the above situation, reporters from Securities Times e Company learned from various interviews from MSD China that the current immunization program for the quadrivalent and nine-valent HPV vaccines listed in China is three doses. The program is based on the approved adaptation of clinical research data in China. disease.

  Merck China said that the vaccination program of the vaccine should be based on strict scientific demonstration. And in 2017 and 2018, it was approved for marketing by the State Drug Administration of China (the former State Food and Drug Administration).

  Merck China further pointed out that the efficacy and safety of two-dose vaccination, single-dose vaccination, or other immunization procedures not approved by regulatory agencies for the Chinese population have yet to be further confirmed.

Merck China recommends that healthcare professionals and consumers follow regulatory-approved HPV vaccine instructions.

  Merck said that the company is committed to protecting the health of Chinese women through HPV vaccines and helping Chinese women of school 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 two-dose immunization programs for adolescents in certain markets outside 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 HPV vaccine supply nearly doubled from 2017 to 2020, and is expected to double again from 2020 to 2023.

  With the increase in global production capacity, Merck's HPV vaccine supply to China is also increasing year by year.

In the first quarter of 2022, the batch issuance of Merck's quadrivalent HPV vaccine increased by nearly 70% year-on-year, and the batch issuance of nine-valent HPV vaccine increased by nearly 280% year-on-year.

Merck said it will continue to increase its supply to the Chinese market to meet the growing demand for HPV vaccines by more women and contribute to the development of public health in China.

  HPV vaccine supply shortfall

  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 in the world.

HPV is directly related to cervical cancer. The HPV vaccine is the first vaccine used to prevent tumors in the world. It is the first time that humans have tried to eliminate a cancer through vaccines.

At present, there are three main types of HPV vaccines commercialized in the world, namely HPV bivalent vaccine, HPV quadrivalent vaccine and HPV nine-valent vaccine.

  At present, the products listed in the domestic market are mainly nine-valent and quadrivalent vaccines imported from Merck, as well as some domestically-produced quadrivalent and bivalent vaccines. The current recommended number of injections is 3 doses.

my country's HPV vaccine market is mainly divided by 4 vaccines, including Xinke Ning (bivalent) from Wantai Bio, Cervarix (bivalent) from GlaxoSmithKline in the United Kingdom, Gardasil (tetravalent) from Merck & Co. price).

  It is worth noting that the quadrivalent HPV vaccine exclusively represented by Zhifei Bio was officially launched on the market in November 2017. The product was sold well in the initial stage of the market, and there was a phenomenon of "rushing for the vaccine".

Subsequently, the nine-valent HPV vaccine has been in a state of "hard to get one shot" after it was launched. All parts of the country need to make an appointment to administer it. At present, the bivalent and quadrivalent HPV vaccines are also in short supply.

  There is still a large gap in the current HPV vaccine supply in my country.

According to Frost & Sullivan's forecast, the overall HPV vaccination rate in my country is low (less than 1%); if the expected increase in the HPV vaccination rate is included, it is estimated that by 2050, there will still be 234 million 9 Women up to age 45 are not vaccinated against HPV.

  In the face of the market in short supply, many domestic companies have joined the ranks of developing HPV vaccines.

  On the evening of March 15, Chengda Biology announced that the 15-valent HPV vaccine developed in cooperation with Recreation Guard has received the "Drug Clinical Trial Approval Notice" approved and issued by the State Drug Administration, and the 15-valent HPV vaccine has been approved for development. Clinical trial; Watson Bio announced on the evening of March 28 that Zerun Bio, an indirect subsidiary of the company, recently received the "Drug Registration Certificate" for the bivalent human papillomavirus vaccine (Pichia pastoris) approved and issued by the State Food and Drug Administration. .

  According to the Huaan Securities Research Report, in the field of 9-valent vaccines, in addition to Recreation Guard and Ruike Bio, Bowei Bio and Wantai Bio have also entered the phase III clinical stage.

In the field of quadrivalent vaccines, there are 3 clinical products. Currently, the fastest progress is Bowei Bio and China Bio, both of which have entered the Phase III stage.

In the field of bivalent vaccines, Watson Bio has made the fastest progress and has entered the stage of marketing application.

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