HPV Vaccine Market in Fierce Competition: Bivalent HPV Prices Plummet While Nonavalent HPV Races Toward Approval

Reporter Sun Mengyuan and Yu Na from chinatimes.net.cn, Beijing Report

As the annual reports of China-produced HPV companies are gradually disclosed, the main trends in the HPV market are coming to light. Based on the annual report data,Walvax、WANTAI BioPharmThe sales of low-price HPV vaccines have fallen short of expectations, while high-price HPV vaccines are in constant competition.

March 29,Health GuardRevealed to the reporter of "Huaxia Times," the company andLiaoning ChengdaBiological ProductsBeijing Health Guard Biotechnology, Inc. and Beijing Wantai Biological Pharmacy Enterprise Co., Ltd. jointly announced that the Phase I clinical trial of their co-developed "Recombinant 15-valent Human Papillomavirus Vaccine (Escherichia coli)" has officially commenced.

　　Involution

HPV stands for "Human Papillomavirus." 99% of cervical cancer cases are caused by high-risk types of HPV, which are mainly transmitted through sexual contact and other routes. The HPV vaccine, as the only vaccine currently available that can prevent cancer, has received widespread attention.

In 2016, GSK's bivalent HPV vaccine entered the Chinese market. In May 2017, MSD's quadrivalent HPV vaccine was approved for marketing in China, dominating the market for a long time. Just two years later, the era of domestic substitutes arrived.

In 2019, WANTAI BioPharm's Cecolin® was approved for marketing, breaking the monopoly of foreign companies at one stroke. WANTAI BioPharm became the pioneer of China’s first domestically produced bivalent HPV vaccine. However, the good times did not last long. With MSD’s age expansion and the nationwide promotion of HPV immunization programs in China, the low-priced HPV market has fallen into a state of underlying turbulence.

In 2022, Walvax's bivalent HPV vaccine, Woze Hui®, was launched, becoming the second domestically produced HPV vaccine approved for marketing in China. In order to capture more market share, both WANTAI BioPharm and Walvax engaged in intense competition through price wars.

In May of that year, in the HPV vaccine bidding in Jiangsu Province, Walvax Biotechnology Co., Ltd. won a bid for 22,400 vials at a price of 246 yuan per vial.

In July 2023, WANTAI BioPharm won the HPV vaccine procurement project in Guangdong Province at a price of 116 yuan per dose, which was more than half off compared to the initial price of 329 yuan per dose in 2022.

On March 22 this year, according to the Jiangsu Government Procurement Network, WANTAI BioPharm won the bid for the procurement of 499,206 doses of bivalent HPV vaccine at a price of 86 yuan per dose. This marks a new historical low following last year's bid win in Guangdong at 116 yuan per dose, representing a significant price reduction of up to 74%. This price also sets a record low for HPV vaccine bids by Chinese manufacturers.

Behind the continuously dropping prices lies the fact that the bivalent HPV vaccine is not selling well.

According to the 2023 annual report released by WANTAI BioPharm, the company achieved revenue of 5.511 billion yuan during the reporting period, a year-on-year decrease of 50.73%; the net profit attributable to the parent company was 1.248 billion yuan, a year-on-year decrease of 73.65%. This is also the first decline in revenue and net profit since the company's listing in 2020. WANTAI BioPharm also admitted in the annual report that the sales of its bivalent cervical cancer vaccine did not meet expectations due to factors such as the expanded age range for the nine-valent cervical cancer vaccine and market competition.

Similarly affected is Walvax. The annual report shows that the company achieved operating revenue of 4.114 billion yuan in 2023, a year-on-year decrease of 19.12%. The net profit attributable to shareholders was 419 million yuan, a year-on-year decrease of 42.44%. The net cash flow generated from operating activities was 1.134 billion yuan, a year-on-year decrease of 5.64%.

Walvax also stated that, due to the expanded age indication and significant increase in import quantities of the nine-valent human papillomavirus (HPV) vaccine, the sales volume of the company's bivalent HPV vaccine (Pichia pastoris) did not meet expectations. The combined impact led to a decline in both revenue and net profit from vaccine products during the reporting period compared to the same period last year.

As the earliest entrant, MSD has not given up on the nine-valent HPV vaccine.

On January 9, MSD (MSD is the trade name of Merck & Co., Inc., located in Rahway, New Jersey, USA) announced that the two-dose vaccination schedule (0.6–12 months) for females aged 9–14 using its nine-valent human papillomavirus vaccine (recombinant yeast) (trade name: Gardasil 9) has been approved by the China National Medical Products Administration. This approval means that, in addition to the previously approved three-dose schedule for ages 9–45, Gardasil 9 will now include a two-dose schedule for females aged 9–14. This move has also been interpreted by the industry as an indirect price reduction for MSD's nine-valent HPV vaccine.

In March this year, MSD announced again its plan to conduct a clinical trial for a single-dose vaccination regimen of the nine-valent HPV vaccine, aiming to evaluate the protective efficacy and safety of the single-dose regimen compared with the already approved three-dose regimen. If successful, the vaccination cost is expected to be further reduced.

　　Speed Competition

　　Huaan SecuritiesThe research report pointed out that China approved the HPV vaccine for the first time in 2017. By 2020, the market size of the HPV vaccine had rapidly grown to 13.5 billion yuan. It is predicted that by 2030, the market size of the HPV vaccine will increase to 69 billion yuan, with a compound annual growth rate of 17.7% from 2020 to 2030.

Apart from MSD's nine-valent HPV vaccine, there are currently no commercially available nine-valent HPV vaccines produced in China. For a long time, the nine-valent HPV vaccine has been in a state of short supply, creating opportunities for domestic companies. According to incomplete statistics, five local companies with relatively faster progress in nine-valent HPV vaccine development include WANTAI BioPharm, Walvax, Health Guard, Jiangsu Ruike Biotech Co., Ltd., and Boer Bio. Their related vaccine products have all entered Phase III clinical trials.

Jiangsu Ruike Biotech Co., Ltd. stated in its 2023 annual report that the recombinant nine-valent HPV vaccine REC603 is currently undergoing Phase III clinical trials in China, with regular follow-ups being conducted according to the clinical protocol. We have completed the 24-month visit and are currently conducting the 30-month visit observation. We will perform an interim analysis using pathological endpoints and submit the BLA application upon meeting the conditions.

According to WANTAI BioPharm's 2023 annual report, during the reporting period, the on-site work for the V8 visit of the Phase III main clinical trial of WANTAI BioPharm's nine-valent HPV vaccine has been completed, and specimen testing is currently underway. The head-to-head clinical trial results with Gardasil 9 have met the expected clinical trial design. The bridging clinical trial for the younger age group has been completed, and the report writing is currently in progress. The construction of the commercial production workshop has been finished, and the industrial scale-up and process validation are proceeding smoothly.

On March 26, Health Guard announced that the Phase III clinical trial of its nine-valent HPV vaccine (for female indications) has entered the case monitoring stage, with visitations currently ongoing for months 30 to 36. If clinical progress is smooth, the company is expected to submit the BLA (Biologics License Application) for the nine-valent HPV vaccine in 2025.

On the same day, Walvax announced that its nine-valent HPV vaccine is currently in Phase III clinical trials. The overall data from the head-to-head clinical trials with similar vaccines is still under statistical analysis. The company will carry out subsequent research and development and related clinical studies according to the latest regulatory requirements. For specific progress, please refer to the company's subsequent disclosed information. The vaccination rate of HPV vaccines in the Chinese market has been continuously increasing in recent years, with some differences in penetration rates depending on various statistical methods, but there is still a significant gap from the target set by the WHO.

Vaccine expert Tao Linapreviously told reporters from our newspaper that, from the perspective of research and development, HPV technology is not difficult. The current issue lies in the fact that the standard R&D cycle has been tightly restricted. In the past, the main requirement was to achieve cancerous lesions at stage two or higher (CIN2) with histopathological changes as the primary endpoint for studies. Therefore, the R&D time for many projects has been extended, leading to a delay in their market launch.

He further pointed out that, according to the newly released guidelines, future iterative vaccines can use 12-month persistent infection (PI12) as a substitute endpoint or the number of cases as the endpoint. Whichever endpoint is reached first can be submitted for market approval. Making appropriate adjustments will also help accelerate the R&D progress.

Zhang Xuefeng also analyzed to our reporter that in the vaccine field, safety, efficacy, and the convenience of vaccination protocols are all key factors for success. Therefore, manufacturers' efforts and innovations in these areas will determine their future position in the market. With the continuous development of the vaccine market, a diversified range of product options will help better meet the needs of different groups, driving companies to continuously enhance their competitiveness.

Editor: He Junxi