Kangle Weishi's Trivalent HPV Vaccine Meets Primary Endpoint in Phase III Interim Analysis: Aiming to Capture the Underserved Self-Paid Market

On August 13, Beijing Health Guard Biotechnology, Inc., a company listed on the Beijing Stock Exchange, announced that the preliminary analysis results of the primary endpoint data from the interim analysis of its Phase III clinical trial for the recombinant trivalent human papillomavirus (HPV) vaccine (types 16/18/58) (E. coli) met expectations. According to the company’s prospectus, the BLA for this trivalent vaccine is expected to be submitted within the year.

Compared with the currently marketed bivalent and quadrivalent HPV vaccines, this vaccine provides additional coverage against HPV type 58. This genotype is the third most common HPV type detected in cervical cancer cases and high-grade lesions in China and East Asia, surpassed only by HPV types 16 and 18. Consequently, this trivalent vaccine increases the protection rate against cervical cancer among East Asian women from 70% with the original bivalent and quadrivalent HPV vaccines to 78%.

Following the successive launches of Wantai’s and Walvax’s bivalent HPV vaccines, these domestic products have gradually eroded the market share of imported bivalent HPV vaccines. In 2023, only 13 batches of imported bivalent HPV vaccines were approved for release in China, whereas Wantai’s bivalent HPV vaccine had 328 batches approved, and Walvax’s bivalent HPV vaccine had 27 batches approved.

Although there are ongoing claims in the market that the HPV vaccine market has reached saturation, data from Frost & Sullivan shows that, as of 2022, the cumulative vaccination rate among women aged 9–45 eligible for HPV vaccination in China was only 9.36%. In contrast, during the same period, female HPV vaccination rates in countries such as Australia, Canada, and Denmark had already reached 80%, 86%, and 82%, respectively. To achieve the World Health Organization’s target of 90% HPV vaccination coverage by 2030, a substantial unmet gap remains.

Currently, cities such as Jinan, Xiamen, and Ordos in China have implemented policies providing free HPV vaccination for school-aged female students, offering low-valent HPV vaccines at no cost. The number of provinces and municipalities offering free vaccination has been increasing year by year.

Recently, Watson won a bid in Shandong Province to supply 1.0162 million doses of bivalent HPV vaccine for RMB 27.9465 million, bringing the winning bid price per dose down to RMB 27.5. Consequently, the topic “HPV Vaccine Costs No More Than a Cup of Milk Tea” quickly trended on Weibo.

However, this price reflects only the government’s subsidized procurement rate; currently, the out-of-pocket market price for the bivalent HPV vaccine in China remains at RMB 325 per dose. Moreover, the share of the public-funded market for HPV vaccines in China lags significantly behind that of the out-of-pocket market, accounting for less than 10% of the total domestic HPV vaccine market.

Once Health Guard’s trivalent HPV vaccine hits the market, it will become a disruptor in the low-priced HPV vaccine segment. Previously, Health Guard stated that the pricing of its trivalent HPV vaccine would be determined in light of market conditions, with an expected price point higher than that of currently marketed bivalent HPV vaccines but lower than that of quadrivalent HPV vaccines. At that time, the competitive landscape of China’s low-priced HPV vaccine market will be reshuffled.

In the high-valent HPV vaccine market, Merck’s GARDASIL 9 is currently the only nine-valent HPV vaccine available in China. Except for the second quarter of this year, it has maintained rapid growth in the Chinese market. The decline in China during the second quarter directly resulted in a mere 1% year-over-year increase in GARDASIL 9’s global sales for that period.

In the subsequent earnings conference call, Merck attributed this to the timing of HPV vaccine shipments in the Chinese market and the ongoing anti-corruption campaign in the healthcare sector in recent years.

Industry experts note that there are multiple critical milestones in the vaccine access and sales processes, which extend the payment collection cycle. As a result, quarterly sales revenue does not accurately reflect the actual sales performance of vaccines during that period. Given that Merck’s HPV vaccine sales in the first quarter of 2024 were still driven by the Chinese market, it is premature to conclude that the market is contracting.

Although no domestically produced nine-valent HPV vaccine has yet been launched in China, several major manufacturers have entered the late stages of Phase III clinical trials, making clinical progress a key focus of public concern.

On August 12, Wantai Bio announced that its nine-valent HPV vaccine had been proposed for inclusion in the priority review list by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). On April 11 of this year, Wantai issued an announcement stating that the Phase III clinical trial results of the nine-valent HPV vaccine met expectations. Given that Wantai previously launched its bivalent HPV vaccine in May 2020, this nine-valent HPV vaccine may be classified as an iterative vaccine under the “Technical Guidelines for Clinical Trials of Human Papillomavirus Vaccines (Trial)” issued by the CDE in 2023, thereby shortening the time to market approval.

The unblinding of the Phase III clinical trial for Health Guard’s trivalent HPV vaccine also signals that its nonavalent HPV vaccine is poised for launch. In accordance with the aforementioned guidelines, Health Guard’s nonavalent HPV vaccine is expected to be submitted for market approval as an iterative vaccine.

Hao Chunli, Chief Operating Officer of Health Guard, stated in an interview that competition among domestic HPV vaccine manufacturers will be multidimensional. “First, low-valent and high-valent HPV vaccines will coexist for a long term, catering to different market demands. Second, competition will begin with female indications and gradually expand into the male indications market. It will further extend to the booster vaccination market. For instance, children who currently receive low-valent HPV vaccines will reach their twenties and gain purchasing power; at that point, will they opt for the 9-valent vaccine?”

HPV infection not only leads to cervical, vulvar, and vaginal cancers in women, but also causes penile, anal, and head and neck cancers in men. Under competitive pressure from domestic vaccine manufacturers, Merck has submitted a marketing application in China for the male indication of its nine-valent HPV vaccine, aiming to capture a share of the domestic male HPV vaccine market. Meanwhile, companies such as Health Guard and Wantai have already laid out strategies for the male indication of their nine-valent HPV vaccines.

Domestic HPV vaccine manufacturers in China have all designed annual production capacities of tens of millions of doses. In Hao Chunli’s view, the Chinese market cannot absorb such substantial capacity, and “these companies will inevitably expand overseas.”

For domestic vaccine manufacturers, current internationalization strategies can be categorized into three approaches: obtaining WHO Prequalification (PQ) certification to access international procurement markets; conducting overseas clinical trials and achieving localized registration and production; and submitting marketing authorization applications in other countries based on clinical trial data generated in China.

Previously, the bivalent HPV vaccines from Wantai and Walvax sequentially received WHO Prequalification (PQ) certification. Meanwhile, Health Guard initiated Phase III clinical trials for the female indications of its nine-valent HPV vaccine in Indonesia in 2023, with plans to submit a marketing application in 2025.

“Given that only two HPV vaccine manufacturers are currently capable of supplying the global market, we believe there remains substantial room for growth in the global HPV vaccine market, presenting a significant opportunity for Chinese enterprises. The challenge lies in the varying regulatory frameworks, legal requirements, and payment capacities across different countries; therefore, we prefer to mitigate risks by collaborating with local partners,” said Jiang Dunquan, Director of Business Development at Health Guard.

“However, given the high HPV vaccination rates in major European and American countries, the international expansion of domestic HPV vaccine manufacturers will continue to focus on developing countries and regions. ‘Vaccination coverage in developed nations is already very high, leaving limited market space. Health Guard will prioritize markets in ASEAN, South America, the Middle East, and Africa,’ said Hao Chunli.”