SILVER SPRING, MD. — In nearly unanimous votes, a Food and Drug Administration advisory panel agreed that data on Gardasil supported the efficacy and safety of the vaccine for use in preventing genital warts caused by human papillomavirus types 6 and 11 in boys and men aged 9–26 years.
At the meeting, the FDA's Vaccines and Related Biological Products Advisory Committee voted 7-0 with 1 abstention on the efficacy question and voted 7-1 on the safety question. The panel was not asked specifically on whether to recommend licensure of Gardasil (human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), manufactured by Merck & Co.
The FDA usually follows the recommendations of its advisory panels. A Merck spokesperson said the company expects the FDA to make a decision during the fall. The vaccine is licensed for use in girls and women aged 9–26 years, for the prevention of cervical, vulvar, and vaginal cancer caused by the oncogenic HPV types 16 and 18, and associated precursor dysplastic lesions (CIN, VaIN, AIS), and genital warts caused by HPV 6 and 11. It has been available since 2006 and is administered in a three-dose series of intramuscular injections at 0, 2, and 6 months.
The expanded indication proposed by Merck is for use in boys and men aged 9–26 years, “for the prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11,” the two HPV types that cause the majority of genital warts.
Gardasil was evaluated in a pivotal safety and efficacy study, a multinational study of approximately 4,000 boys and men aged 16–26 years, who received Gardasil or placebo; 85% were hetero-sexual and 15% were men having sex with men. Participants with a history of genital warts, no history of sexual activity, and those with more than five lifetime sexual partners were excluded.
The primary end point was the effect of the vaccine on the combined incidence of HPV 6/11/16/18–related external genital lesions (EGL), which included external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), and penile, perianal, or perineal cancer.
In the approximately 1,800 subjects who received all three Gardasil doses and were tested at month 7, the vaccine was 90% effective in preventing HPV 6/11/16/18–related EGL, a highly statistically significant effect. The vaccine was 89% effective in preventing condylomata acuminata, the focus of the proposed indication. There were few cases of PIN and no cases of cancer in either placebo or Gardasil recipients.
A study of adolescent boys aged 9–15 years and of boys and men aged 16–26 years who received the three Gardasil doses determined that the immune responses to each of the four HPV types among the younger participants was not inferior to the responses seen among those in the older group.
In the pivotal trial, the number of adverse events reported within 1–15 days of any of the vaccinations was 10% higher (74% vs. 64%) among Gardasil recipients, mostly due to injection site–related adverse events (the most common was injection-site pain). Systemic adverse events were slightly more common in the vaccine group; no serious adverse events were attributed to the vaccine. More than 95% of the adverse events were mild to moderate. In the safety database of about 5,400 boys and men, no safety signals have been identified, according to the FDA.