On October 26, the Drug Review Center of the State Food and Drug Administration issued a notice on public soliciting opinions on the "Technical Guidelines for Clinical Trials of Human Papillomavirus Vaccine", pointing out that HPV vaccine has a long research and development cycle

China Times (www.chinatimes.net.cn) reporter Sun Mengyuan Yu Na Beijing report

htmlOn October 26, the National Drug Administration Drug Review Center (CDE) issued a notice on public soliciting opinions on the "Technical Guidance Principles for Clinical Trials of Human Papillomavirus Vaccine (Draft for Comments)" pointed out that the HPV vaccine has a long R&D cycle and high R&D costs, in order to guide vaccine companies to standardize R&D and accelerate the market of related products. The guiding opinion of

was interpreted by the industry as "the relevant national management departments encouraged the domestic replacement of HPV vaccines and encouraged more domestic HPV vaccines to accelerate the market launch process."

may be affected by this news. Zhifei Bio, which is a proxy for importing Merck quadrivalent HPV and nine-valent HPV vaccines, suffered a major impact in the secondary market. It once fell by more than 17% during the session. As of the closing on the 27th, it closed at 86.48 yuan per share, a drop of 10.48%. A relevant person in charge of Zhifei Bio told the China Times reporter that the company did notice this document, but the reason for the decline in the stock price is still unclear, and the company's operations are currently normal.

stock price plummeted

On October 26, the CDE released the "Technical Guidance Principles for Clinical Trials of Human Papillomavirus Vaccine (Draft for Comments)", which is applicable to preventive vaccines that are intended to be listed in China and assembled as virus-like particles (VLP) with the main capsid protein L1 of HPV. Perhaps due to this news, as the exclusive agent of imported HPV, Zhifei Bio suffered a heavy blow in the secondary market.

This guiding principle sorts out and summarizes common problems in HPV vaccine application and clinical trials, and conducts a survey on the clinical research progress and related technical requirements of HPV vaccines at home and abroad. The guiding principle first introduces the overall considerations of indications, R&D strategies, and applicable populations, and then explains the key points of design and evaluation according to different clinical trial stages.

Relevant person in charge of Zhifei Bio told the reporter of the China Times that the company did notice this document, but the document is still solicited for manuscripts. The specific impact cannot be analyzed in detail. I have paid attention to today's stock price, but the reason for the decline is still unclear. The company's operations are currently normal.

Zhifei Bio is the exclusive agent of Merck's quadrivalent and nine-valent HPV vaccines in China and is known as the leading company in domestic HPV vaccines.

Since 2018, Zhifei Bio has exclusively represented the launch and sales of two HPV vaccines from Merck in the mainland Chinese market. Although the revenue performance of HPV vaccines was not disclosed in the financial report, the HPV vaccine batch issuance has been increasing year by year. From 2018 to the first half of 2022, the batch issuance of its quadrivals HPV vaccines was 3.800273 million, 5.543719 million, 7.219462 million, 8.8025 million, and 4.876778 million, respectively, and the batch issuance of its nine-valent HPV vaccines was 1.216102 million, 3.324173 million, 5.066376 million, 10.206168 million, and 9.298758 million, respectively.

According to the third quarter report of Zhifei Bio on October 27, during the reporting period, the company's main agent products increased significantly, with 11.81 million quadrivalent HPV vaccines being issued, and increased by 4158% year-on-year; 12.28 million numerical HPV vaccines being issued, a year-on-year increase of 128%.

Based on this calculation, from 2018 to September 2022, the batch issuance of Zhifei Bio's HPV vaccine exceeded 80 million.

It is worth mentioning that the term of the agency agreement between Zhifei Bio and Merck is from 2021 to June 2023. It is still unknown whether the contract will be renewed in the future. The above-mentioned person in charge of Zhifei Bio told the China Times reporter, "The cooperation with Merck will be until June next year. Whether the company's business department will negotiate with Merck in the future. If there is any news, the announcement will be issued as soon as possible."

Regarding whether it will be represented in the domestic HPV vaccine or develop and produce HPV vaccines in the future, the person in charge said that there is no news about this at the moment.

domestic vaccine may be launched at a faster pace

At present, there are 5 HPV vaccines approved in the domestic market, three imported vaccines are Merck's quadrivalent vaccine "Jadarxiu", nine-valent vaccine "Jadarxiu 9", and GlaxoSmithKline bivalent vaccine "Xiruishi"; the two domestic vaccines are Wantai Biological's bivalent vaccine "Xinkening" and Watson Bio's bivalent vaccine "Wozehui".Although domestic bivalent HPV vaccines have begun to increase in volume and accelerate the supply market, domestic nine-valent HPV vaccines have not yet been launched.

high-priced HPV vaccine has a prominent contradiction in supply and demand, and domestic pharmaceutical companies are making every effort to accelerate research and development.

According to incomplete statistics, as of the end of February 2022, there were about 16 domestic HPV projects under development. The local companies that have made rapid progress in nine-valent HPV vaccines include Wantai Bio, Watson Bio, Bowei Bio, Kangle Guardian, and Ruike Bio, all of which have entered the Phase III clinical stage; the higher-priced vaccines under development include the 14-valent HPV vaccine of Shenzhou Cell, the 15-valent HPV vaccine of 3 Chloro Biotechnology , and the 11-valent HPV vaccine of China Pharmaceutical Group .

This guidance is undoubtedly good news for companies that are developing HPV vaccines. In an interview with a reporter from the China Times, Tao Lina, a vaccine expert at

, said that from the perspective of R&D level, HPV technology is not difficult. The current problem is that the routine R&D cycle is too stuck. The past requirement was mainly to reach the level 2 or above of cancer disease (CIN2) and pathology of changes cases as the main research endpoint, so many R&D time will be extended and the time to market will be extended.

He further pointed out that according to the newly released guiding principles, in the future iteration of vaccines can use 12 months of continuous infection (PI12) as a replacement indicator, or use the number of incidence as the end indicator. Any indicator that comes first can be applied for market. If some adjustments are made appropriately, the R&D progress will also be accelerated.

Wantai Biological's third quarter report shows that the company's nine-valent HPV vaccine Phase III clinical trial and industrial amplification are progressing smoothly. The head-to-head clinical trial with Jiadaxiu 9 has completed the clinical trial site and specimen testing work, and is undergoing statistical analysis of data. The small-age bridged clinical trial has completed the enrollment work, the construction of a commercial production workshop has been completed, and the industrial amplification production research is underway.

"The company's nine-valent HPV vaccine is an iterative product. The current clinical design and guiding principles ( draft for soliciting opinions ) are consistent, and it can be applied for early market with 12 months of continuous infection." Wantai Biologics told the reporter of the China Times.

Watson Bio also mentioned in its third quarter report that the company's nine-valent HPV vaccine has entered the Phase III clinical research stage in September and is currently carrying out various work on enrollment of subjects.

The nine-valent HPV vaccine developed by Shanghai Bowei Bio launched a phase III clinical trial in April 2020. This is also the first domestic HPV nine-valent vaccine to enter the phase III clinical trial in my country. The relevant person in charge of

Kangle Guard had previously revealed to a reporter from the China Times that the Phase III clinical trial of the company's nine-valent HPV vaccine (female indication) under research project has completed three doses of vaccination and started case monitoring and follow-up. The small-age group immune bridging clinical trial has completed subject enrollment. The nine-valent HPV vaccine (male indication) under research project has completed the Phase I clinical third dose of vaccination, and is currently conducting the 7th month follow-up.

China Securities' previous research report believes that the competitive landscape of two imports + two domestic products will remain stable in the short term, and the penetration rate of HPV vaccine is expected to increase rapidly with the release of in production capacity. In the medium and long term, the 9-valent pipeline of many domestic vaccine companies has been advanced to phase III of clinical practice. Expression systems, new adjuvants, etc. will also promote the iteration of HPV vaccine products, differentiated competition between domestic and imported products, and share the vast domestic stock market.

Intern editor: Yan Yuan Editor-in-chief: Chen Yanpeng