The expanded approval of the currently marketed human papillomavirus vaccine to women aged 27–45 years is being held up, at least until the manufacturer addresses some outstanding issues.
In a statement issued in late June the manufacturer of Gardasil, Merck & Co., announced that the Food and Drug Administration had advised the company that there were issues that precluded approval of the vaccine for the older age group within the time frame that had been specified for the FDA's review to be completed.
The company has discussed the FDA's questions with the agency and at press time was expected to respond to the issues raised, according to Merck's statement. Neither the company nor the FDA elaborated on the specific issues.
In 2006, Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, 18] Vaccine, Recombinant) was approved for girls and women aged 9–26 years for prevention of cervical cancer, precancerous or dysplastic lesions, and genital warts caused by HPV types 6, 11, 16, and 18.
The FDA designated the review of Gardasil in the older age group as a priority review in March. Data from clinical trials in older women were presented by Merck at the winter meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention. In placebo-controlled studies on Gardasil, including one study of almost 4,000 women aged 24–45 years, two-thirds of the women were negative for all four HPV serotypes in the vaccine, and about one-third were positive for one or more of the HPV vaccine serotypes; only 0.4% of the vaccine recipients and 0.3% of the controls were positive for all four.
Over a mean follow-up of 2.2 years, primary efficacy of the vaccine against persistent infection, cervical intraepithelial neoplasia, or external genital lesions caused by any of the four vaccine strains was 92% among subjects aged 24–34 years and 89% among 35- to 45-year-olds. Efficacy against cervical intraepithelial neoplasia or external genital lesions caused by any of the four vaccine serotypes was 92% (88% for 16 and 18, 100% for 6 and 11). Safety profiles were similar to those seen in the 16- to 26-year-old age group, with no serious vaccine-related adverse events among vaccine recipients.