Nine-valent HPV vaccine age expansion, domestic vaccine research and development accelerated, who will be "China Merck"?

From the age of vaccination from 16-26 years to 9-45 years, the expansion of merck's nine-valent HPV vaccine indications has attracted widespread attention

Cervical cancer is the second largest tumor disease in women in the world and the second largest tumor disease

At present, among the domestic HPV vaccines in China, the bivalent HPV vaccine under Wantai Biologics and the bivalent human papillomavirus vaccine (HPV2 vaccine) independently developed and produced by Yuxi Zerun, a subsidiary of Watson Biology, have been approved for marketing by

In the domestic market, the supply and demand situation of HPV vaccines of different prices is also different

The shortage of nine-valent HPV vaccine extended age vaccine remains to be solved

The world's first HPV vaccine was approved for marketing

Bivalent, quadrivalent, and nine-valent HPV vaccines can prevent HPV16 and type 18 infections (the two main HPV types that cause cervical cancer, together causing about 70% of cervical cancer), quadrivalent HPV vaccines can also prevent HPV6 and 11 infections (both cause about 90% of genital warts together), and the nine-valent HPV vaccine can also provide protection for another 5 high-risk HPV infections compared with quadrivalent HPV vaccines (the 5 high-risk HPV types together cause about 20% of cervical

In the domestic market, the supply and demand situation of HPV vaccines of different prices is also different

▲Zhifei Bio's 2022 semi-annual report

In the global HPV vaccine market, quadrivalent and nine-valent HPV vaccines are currently controlled by Merck with the world's most core production capacity and pricing power

The data shows that in the first half of the year, the batch issuance volume of MERCK Quadrivalent and 9.

Currently, the nine-valent HPV vaccine uses a three-dose immunization program

Previously, Guosen Securities released a research report that about 360 million women of the appropriate age aged 9-45 in China, since the introduction of HPV products in China in 2017, the total number of batch issuances has been about 65 million, the number of contracts is 20 million, and the overall population penetration rate is about 5.

This means that behind the expansion of HPV nine-valent vaccine, the situation of "one shot is difficult to find" for nine-valent vaccines still needs to be alleviated

However, the number of nine-valent vaccines imported from home continues to increase

▲Zhifei Bio's 2020 annual report data

A variety of domestic HPV nine-valent vaccines into the clinical phase III who will become China's "Merck"?

In the international HPV vaccine track, although Merck and GSK have long monopolized the global cervical cancer vaccine market, there have been two bivalent HPV vaccines on the market in China, and many vaccine companies are also racing against time to carry out research and development and clinical trials

Shell financial reporter learned that it is understood that the HPV nine-valent vaccine of Watson Bio (Shanghai Zerun), Wantai Bio (Beijing Wantai Bio), Shanghai Bowei, Kangle Guardian and Ruike Bio has entered the third phase of clinical practice
.

On August 26, the listed company Wantai Bio released a semi-annual report mentioning that "the phase III clinical trial and industrialization of the nine-valent HPV vaccine are progressing smoothly", and the head-to-head clinical trial of the company's nine-valent HPV vaccine and Jiada Xiu 9 has completed the clinical trial site and specimen testing, and is undergoing statistical analysis of data, and the small age bridging clinical trial has completed the enrollment work
.

Wantai Bio said that in order to accelerate the commercialization process of the nine-valent HPV vaccine, it has completed the installation and commissioning of the production workshop and smoothly entered the process transfer stage, laying a solid foundation
for subsequent process verification and declaration of production.

In addition, Wantai Bio's Phase II expansion and construction project of the nine-valent cervical cancer vaccine and the construction of the nine-valent cervical cancer vaccine base (Phase I) are all in progress as planned
.

According to the semi-annual report of Wantai Biology, as of the end of June this year, the cumulative actual investment amount of the nine-valent cervical cancer vaccine base construction (phase I) project is 530 million yuan, and the cumulative actual investment amount of the nine-valent cervical cancer vaccine phase II expansion construction project is 304.
378 billion yuan
.

On August 9, ruike biology, a listed company, issued an announcement disclosing the progress of clinical trials of HPV helivalent vaccine, saying that the company has recently completed the immune bridging of its recombinant nine-valent HPV vaccine REC603 in the small age group and the enrollment and first dose of all subjects in the two studies compared with Gardasil®9 immunogenicity
.
At the same time, subjects in the REC603 main potency trial are being followed up according to the clinical protocol
.

Ruike Bio said that the completed Phase I clinical data show that REC603 is safe and tolerant, with good immunogenicity
.
REC603 uses the Hanson yeast expression system to achieve high yield and stable expression of HPV virus-like particles, making the company's vaccine candidate more suitable for commercial production
.
With clear key process parameters and control strategies, the REC603 is easy to scale up to meet the needs of the domestic and global markets
.

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

It is worth noting that in March this year, Watson Biological Subsidiary Yuxi Zerun Bivalent HPV Vaccine obtained the "Drug Registration Certificate" in March, the first batch of products in May obtained the "Biological Products Batch Issuance Certificate", and in the first half of the year, Yuxi Zerun Bivalent HPV Vaccine was approved and issued 884664.

▲ Watson Bio's 2022 semi-annual report, the number of vaccines issued by it
.

In addition, the phase III clinical trial of the nine-valent vaccine of Shanghai Bowei is still in
progress.
Shell financial reporter noted that in May this year, Guangdong Yangchun Disease Control also released volunteer recruitment information, saying that bowei tetravalent human papillomavirus (HPV) vaccine persistent immunization clinical research project is about to start, the bidder is Shanghai Bowei Biotechnology Co.
, Ltd.
, the responsible institution is Guangdong Provincial Center for Disease Control and Prevention, Guangdong Institute of Biological Products and Pharmaceuticals, the site is located in Yangchun City Center
for Disease Control and Prevention.

How long will the domestic nine-price wait? Connaught Guardian: It is expected to be approved for listing in 2027

The research and development of the nine-valent HPV vaccine of many enterprises in China has entered the clinical phase III stage, so how far is it from being listed?

Taking Connaught Guardian, which also entered the clinical phase III trial, as an example, the company introduced in the semi-annual report disclosed on August 6 that the company launched a clinical trial of immunization in the small age group of the nine-valent HPV vaccine in March, and is currently conducting a phase III clinical trial of the nine-valent HPV vaccine (female indication), and has completed three doses of vaccination of subjects during the reporting period
and is carrying out case surveillance follow-up.

According to Connaught Defender, the purpose of the clinical trial of immune bridging in the small age group of women with nine-valent HPV vaccine is to evaluate the safety and immunogenicity of the nine-valent HPV vaccine in healthy adolescent women aged 9-19 years, and to investigate the non-inferiority of the immune response induced in adolescent women compared with the immune response induced in healthy adult women aged 20-26 years, and the persistence of the immune response
.

In contrast, the nine-valent HPV vaccine of Wantai Biologics and the HPV vaccine of Ruike Biology have completed the clinical trial of small age bridging, and the enrollment and first dose of vaccination of
patients in the immune bridge of small age groups have been completed.

After completing the three doses of vaccination of the subjects, it is also necessary to enter the testing phase
.
In the prospectus issued by Connaught Guard in March this year, it was mentioned that the company's phase III clinical trial of the nine-valent HPV vaccine (female indication) required nine follow-up visits during the case monitoring phase, and the interval between each follow-up was 6 months
.

"The company plans to conduct interim analysis of phase III clinical trials
after completing the 6th case surveillance follow-up in 2025.
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 indications), and the nine-valent HPV vaccine (female indications) will be officially approved for marketing
in 2027.
”

It is worth mentioning that the research project of Connaught Guardian's nine-valent HPV vaccine (male indications) 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 interim analysis of the phase III clinical trial after completing the fifth case surveillance follow-up at the end of 2025, complete the follow-up of all subjects and submit BLA applications by the end of 2027, and expect the nine-valent HPV vaccine (male indication) to be officially approved for marketing
in 2028.
" Wellness Guard said
.