Disease Analysis: Human Papillomavirus (HPV) Vaccines

Disease Overview

HPV is a member of the papillomavirus family, which are known for causing warts. Over 200 different types have been identified so far, and while most HPV infections are not harmful, persistent infection with certain HPV strains can cause anogenital warts and lesions, which if untreated may become cancers. HPV infection is the major cause of cervical cancers, with almost all cases (99%) being caused by HPV infection. Other cancers related to HPV include cancers of the vulva, vagina, penis, or anus. Only about 14 HPV strains are considered high risk for causing cervical cancer, and of these the two most common types, HPV 16 and 18, are responsible for causing around 70% of all cervical cancers globally.

Latest key takeaways

• Approximately 79 million Americans are infected with human papillomavirus (HPV) at any given point, with 14 million people becoming newly infected each year. HPV is spread primarily by vaginal or anal sex, and persistent infection with certain HPV strains can cause anogenital warts and lesions, which if untreated may become cancers. There are currently three branded vaccines for HPV: Cervarix, Gardasil, and Gardasil 9. Merck & Co’s Gardasil, a quadrivalent vaccine, was first-to-market with its debut in 2006, narrowly ahead of the 2007 release of GSK’s rival bivalent vaccine, Cervarix. Both vaccines are based on the recombinant expression of major capsid antigen L1 from different HPV serotypes, which self-assemble into virus-like particles (VLPs). In 2014, Merck & Co’s Gardasil 9, a nine-valent vaccine capable of providing protection from an additional 20% of HPV-related cancers, superseded Gardasil.
• Since the launch of the first HPV vaccine in 2006, the market has seen steady growth, with global sales rising from $235m in 2006 to $5.7bn in 2021. This growth has been attributed to the launch of vaccination programs in most major markets, centered on the treatment of girls aged 9–14 years and catch-up vaccinations for females aged 15–26 years. In the last three years, the HPV market has experienced unprecedented growth, and this upwards trajectory looks set to continue. Key growth drivers include the expansion of vaccination programs to include males aged 9–26 years in major markets such as the US, UK, France, and Germany, rising pressure to increase coverage rates for HPV vaccination globally, and the introduction of national programs in new markets such as China. Indeed, Merck & Co attributed its $850m sales boost in 2018 to a successful launch in the Chinese market. The introduction of additional national HPV vaccination programs is projected to sustain considerable growth in the HPV market, so much so that Merck & Co has invested $1.68bn into two manufacturing plants to meet global demand for HPV vaccination.
• However, there remain significant factors that will limit growth of the HPV market over the next five years. One such factor is that vaccine manufacture is currently lagging behind global demand. To combat this, Merck & Co has announced plans to establish two new manufacturing plants that should be completed by 2023. The Gardasil franchise has always held market leader status because of its wider serotype coverage and preferential reimbursement from payers, and with little competition from Cervarix or any major threats from pipeline candidates, it will maintain its lead for the foreseeable future.
• Cervarix was the second-to-market vaccine and has experienced a sharp decline in sales from a peak of $800m in 2011, triggered by direct competition with Gardasil over market share. The global sales gap between the Gardasil franchise and Cervarix has continued to widen, from $398m in 2011 to $5.5bn in 2021, driven largely by preference for Gardasil 9 in major and emerging markets, and this trend is expected to persist as Gardasil 9 continues to gain uptake in the lucrative Chinese market. Sales of Cervarix bounced back from $68m in 2019 to $180m in 2021, although this remains well below previous peak revenues. While Cervarix will continue to lose share in major markets, the rise of emerging markets presents opportunities for growth in the near future. In particular, a shortage of supply of Gardasil 9 in emerging markets has presented GSK with a small window of opportunity to drive use of Cervarix until Merck & Co can increase its supply of Gardasil 9 to meet growing demand.
• At the end of 2019, China’s regulator approved Cecolin, a generic HPV bivalent vaccine produced by the Chinese firm Innovax. The generic vaccine is set to be the first of a series of vaccines developed by the company, including generics for the quadrivalent and nonavalent HPV vaccines. Datamonitor Healthcare’s discussions with KOLs have indicated that there are several companies generating HPV vaccines in China and India, but approvals of these vaccines in the US and EU are unlikely.
• There is currently only one pipeline candidate in clinical development in the US. GSK4106647A (HPV9-AS04) is a recombinant protein-adjuvanted vaccine being developed by GSK which entered into a Phase I/II trial (ClinicalTrials.gov identifier: NCT05496231) in August 2022, investigating safety and immunogenicity in females aged 16–26 years old.