Beijing News (Reporter Zhang Xiulan) On the evening of August 30, the website of the State Food and Drug Administration showed that the indications of Merck's nine-valent human papillomavirus vaccine (Saccharomyces cerevisiae) (hereinafter referred to as the nine-valent HPV vaccine) have been expanded, and the applicable population has been expanded to Females aged 9-45 are vaccinated.

The vaccine was previously approved for use in women aged 16-26.

　　On the same day, Merck also announced that the new indication of the nine-valent HPV vaccine was approved by the State Food and Drug Administration.

　　About 98% of cervical cancers in my country are caused by high-risk HPV

　　Cervical cancer is one of the common gynecological malignancies.

The 2021 ICO/IARC report on HPV and related diseases in China shows that in 2020, among women aged 15-44 in China, the incidence and mortality of cervical cancer will both rank third among female tumors.

In China, about 98% of cervical cancers are caused by high-risk HPV. Although HPV16 and 18 are high-risk HPVs that are widely prevalent around the world, there are differences in China. The epidemiological study of China shows that the most susceptible high-risk HPV types in Chinese women are HPV16, 52, and 58.

　　The nine-valent HPV vaccine uses a three-dose immunization schedule and is suitable for the prevention of cervical cancer caused by HPV types 16, 18, 31, 33, 45, 52 and 58; HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 Cervical intraepithelial neoplasia (CIN1/2/3) and cervical adenocarcinoma in situ (AIS); and persistent infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

　　WHO releases Global Strategy to Accelerate Cervical Cancer Elimination

　　Professor Qiao Youlin from the School of Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College pointed out that HPV vaccination of adolescent girls is easy to stimulate a better immune response, and women who have not had sex with HPV vaccine will get the best preventive effect.

　　As women age, women's ability to clear new and previous HPV infections decreases, making them more susceptible to persistent HPV infection and cervical cancer risk.

Studies have shown that the HPV vaccine also provides good protection for women who have already had sex.

　　On November 17, 2020, the World Health Organization (WHO) released the "Global Strategy to Accelerate the Elimination of Cervical Cancer", proposing that by 2030, 90% of girls should be vaccinated against HPV before the age of 15, which is also the number of 194 worldwide. For the first time, countries have made a joint commitment to eliminate a cancer.

Vaccination, screening and treatment are three key measures to eliminate cervical cancer.

Qiao Youlin previously pointed out in an interview with a reporter from the Beijing News that to eliminate cervical cancer, screening must be passed in the short term, and in the long run, vaccination must be used.

　　Follow 1

　　Nine-valent HPV vaccine is "hard to find" for a long time

　　Bivalent, quadrivalent, and 9-valent HPV vaccines can prevent HPV16 and 18 types of infection, and quadrivalent HPV vaccine can also prevent HPV6 and 11 types of infection. Compared with quadrivalent HPV vaccine, 9-valent HPV vaccine can also prevent 5 other high-risk protection against HPV infection.

　　In the domestic market, the supply and demand of HPV vaccines at different prices are different.

　　In the global HPV vaccine market, Merck currently holds the world's most core production capacity and pricing power for quadrivalent and nine-valent HPV vaccines.

In 2012, Zhifei Bio signed an exclusive agency agreement with Merck, and Merck exclusively supplied HPV vaccine to Zhifei Bio in mainland China.

　　According to the data, in the first half of the year, the batches of MSD's quadrivalent and 9-valent vaccines represented by Zhifei Biological were 4,876,700 and 9,298,700 respectively.

　　The current nine-valent HPV vaccine uses a three-dose immunization schedule.

From this point of view, the 9.299 million doses of vaccines issued in mainland China in the first half of the year can be provided to about 3 million women for vaccination.

　　Guosen Securities previously released a research report that there are about 360 million domestic women aged 9-45 years old. Since the introduction of HPV products in China in 2017, the total number of batches issued is about 65 million, which is equivalent to about 20 million copies, and the overall population penetration rate is about 20 million. 5.5%, still low.

　　This means that behind the expansion of the age of the HPV nine-valent vaccine, the "hard to get one shot" situation of the nine-valent vaccine still needs to be alleviated.

　　However, the number of domestically imported nine-valent vaccines continued to increase.

According to the data, in 2020, Merck's quadrivalent HPV vaccine was issued in batches of 7.2194 million; the nine-valent HPV vaccine was issued in batches of 5.066 million.

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　　Several domestic HPV nine-valent vaccines enter clinical phase III

　　There are already two bivalent HPV vaccines on the market in China, and many vaccine companies are also racing against time to conduct research and development and clinical trials of HPV nine-valent vaccines.

　　The reporter learned that the HPV nine-valent vaccines of Watson Bio (Shanghai Zerun), Wantai Bio (Beijing Wantai Bio), Shanghai Bowei, Recreation Guard and Ruike Bio have all entered the clinical phase III.

　　On August 26, the listed company Wantai Bio released its semi-annual report, which mentioned that "the phase III clinical trial and industrialization of the nine-valent HPV vaccine are progressing smoothly", and the company's nine-valent HPV vaccine and the head-to-head clinical trial of Jiadaxiu 9 The trial has completed the clinical trial site and specimen testing, and is in the process of statistical analysis of data. The small-age bridging clinical trial has completed the enrolment work.

　　On August 9, the listed company Ruike Bio released an announcement to disclose the clinical trial progress of the HPV nine-valent vaccine, saying that the company has recently completed the immune bridging of its recombinant nine-valent HPV vaccine REC603 in a small age group and compared the immunogenicity with Gardasil 9. Enrollment and first-dose vaccination of all subjects in this study.

At the same time, the subjects of the REC603 main efficacy trial are being followed up according to the clinical protocol.

　　According to the latest semi-annual report disclosed by the listed company Watson Bio on August 11, the subsidiary Shanghai Zerun 9-valent HPV vaccine is also in the clinical research stage, and is currently carrying out the relevant preparations before the subjects of the phase III clinical study are enrolled. Work.

　　In addition, Shanghai Bowei's Phase III clinical trial of the nine-valent vaccine is still in progress.

　　Follow 3

　　RecreationGuard's nine-valent HPV vaccine is expected to be approved for marketing in 2027

　　The nine-valent HPV vaccine research and development of many companies in my country has entered the clinical phase III, how far is it from the market?

　　Taking Recreation Guard, which also entered the Phase III clinical trial, as an example, the company introduced in its semi-annual report disclosed on August 6 that the company launched a nine-valent HPV vaccine immune bridging clinical trial in a small age group in March, and is currently conducting a nine-valent HPV vaccine. Phase III clinical trial of HPV vaccine (female indication), three doses of subjects have been vaccinated during the reporting period, and case monitoring and follow-up are being carried out.

　　According to Recreation Guard, the purpose of the nine-valent HPV vaccine female small age group immune bridging clinical trial is to evaluate the safety and immunogenicity of the nine-valent HPV vaccine in healthy adolescent girls aged 9-19, and to investigate its induction in adolescent girls. Noninferiority of the immune response compared to the immune response induced in healthy adult women aged 20-26 years, and the durability of the immune response.

　　In comparison, Wantai Bio's nine-valent HPV vaccine and Ruike Bio's HPV vaccine have completed the enrollment of small-age bridging clinical trials, and the enrollment and first-dose vaccination of immune bridging subjects in the small-age group.

　　After completing the three-dose vaccination of the subjects, it is necessary to enter the monitoring phase.

According to the prospectus released by Recreation Guard in March, the company's nine-valent HPV vaccine (female indication) Phase III clinical trial will require 9 follow-up visits in the case monitoring phase, with an interval of 6 months for each follow-up.

　　"The company plans to complete the 6th case monitoring follow-up in 2025, and then conduct an interim analysis of the Phase III clinical trial. The company expects to complete the follow-up of all subjects by the end of 2026 and submit a BLA application for the nine-valent HPV vaccine (female indication) in 2027. The nine-valent HPV vaccine (for female indications) was officially approved for marketing."

　　Recreation Guard's nine-valent HPV vaccine (male indication) research project has entered Phase I clinical trials, and the fifteen-valent HPV vaccine has obtained a clinical trial approval notice from the State Food and Drug Administration.

　　"The company plans to complete the 5th case monitoring follow-up at the end of 2025, conduct an interim analysis of the Phase III clinical trial, complete the follow-up of all subjects and submit a BLA application by the end of 2027, and expects a nine-valent HPV vaccine (male indication) in 2028. Officially approved for listing." Recreation Guard said.

　　This group of manuscripts written /

　　Beijing News reporter Li Yunqi