Merck & Co's HPV vaccine protects older women
This article was originally published in Scrip
Women aged 24-45 years who are not already infected with the human papillomavirus (HPV) types that cause most cervical cancers can benefit from Merck's Gardasil, according to Phase III trial results.
Gardasil is a quadrivalent vaccine designed to protect against HPV types 6, 11, 16 and 18, which account for over 70% of cervical cancer cases. In 2006 the vaccine was approved by the US FDA for prevention of cervical cancer and genital warts caused by HPV in females aged nine–26, and it has since been approved and adopted in many other countries. Merck has filed for authorisation to market Gardasil for women aged 27–45, but the FDA delayed approval and requested additional data earlier this year (scripnews.com, January 12th, 2009).
Results of FUTURE III – a randomised, double-blind Phase III trial assessing the vaccination of women aged 24-45 years with Gardasil – were published online on June 1st in The Lancet. Over 3,800 subjects, none of whom had a history of cervical disease, cervical cancer or genital warts, were vaccinated with either Gardasil or placebo at day one, month two and month six. Two primary endpoints were: six month's or more duration of HPV infection and cervical and external genital disease due to any of the four subtypes, HPV 6, 11, 16 and 18; and the same but due to subtypes HPV 16 and 18 only.
Analysis of more than 3,200 subjects who tested negative for the relevant HPV types at day one and at month seven and who received full vaccination showed that the vaccine efficacy for the first co-primary endpoint was 90.5% (95% CI 73.7-97.5) – four cases of infection or disease due to one of the four strains examined occurred in the treatment group, compared with 41 cases in the placebo group. Vaccine efficacy for the second co-primary endpoint was 83.1% (CI 95% 50.6-95.8) – four cases of infection or disease due to HPV 16 or 18 occurred in the treatment group, compared with 23 cases in the placebo group. On the basis of these results, the authors of the Merck-funded study conclude that: "The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment."
For the first and second co-primary endpoints in the intention-to-treat population, which included women who were not completely vaccinated or who had pre-existing HPV infections, vaccine efficacies were 31% (95% CI 11.1-46.5) and 24% (CI 95% –2.9-41.9), respectively. The authors add that most HPV-positive women who enrolled in the study were positive for only one HPV type, and so can still gain some benefit from Gardasil. Yet because the vaccine is not as effective for women who already have HPV or HPV-associated disease, the authors note that future cost-benefit analyses are required to assess the value of vaccinating women aged 25-45 years.
No vaccine related serious adverse events were reported. Whereas the duration of the study will be four years, these results represent an average follow-up time of 2.2 years.
GlaxoSmithKline's HPV vaccine, Cervarix, has been approved in the EU member states and in other countries for females aged 10-45 years, but has not yet been approved by the US FDA. Although the vaccine only includes HPV 16 and 18, recent results from a Phase III trial suggest that it also provides protection against other HPV types. The same trial showed that Cervarix induces a superior immune response than Gardasil (scripnews.com, May 13th, 2009).
Last month, Gardasil received approval from the World Health Organization's prequalification unit, meaning the vaccine can be purchased by UN bodies for use in developing countries (scripnews.com, May 27th, 2009).
Other HPV vaccines are in development: Merck & Co's nine-valent V503 is currently in a Phase III trial.