ATLANTA Merck & Co.'s human papillomavirus vaccine Gardasil was efficacious against persistent infections and genital warts caused by the vaccine strains, in a randomized, double-blind, placebo-controlled study of more than 4,000 adolescent and young adult males.
The study, funded by Merck, was planned as a 36-month follow-up but was stopped early based on efficacy and safety data at a mean of 29 months, according to Dr. Richard M. Haupt, executive director of clinical research, Merck Research Laboratories, Whitehouse Station, N.J. The company submitted a biologics licensing application to the Food and Drug Administration in December 2008 for the use of Gardasil in males aged 9-26 years.
Of the four HPV strains in Gardasil, HPV-16 and HPV-18 are responsible for the majority of HPV-related penile, anal, and oropharyngeal cancers and their associated precancers in males. The other two strains, HPV-6 and HPV-11, cause more than 90% of genital warts and recurrent respiratory papillomatosis.
"Gardasil is highly efficacious against HPV-6/11/16/18-related persistent infections and genital warts in men. This efficacy may also translate to reduced transmission of vaccine type strains between sexual partners," Dr. Haupt said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
The study included 3,463 heterosexual men aged 16-23 years and 602 men aged 16-26 years who have sex with men. Participants with more than five lifetime sexual partners were excluded. At baseline, just 17% of the total group was positive to at least one of the vaccine HPV strains by either serology or polymerase chain reaction testing, meaning that a large majority (83%) was susceptible.
The primary end point was vaccine efficacy against all external genital lesions.
In the per-protocol population, overall efficacy was 90%, driven primarily by the prevention of genital warts: 28 of 1,408 placebo subjects developed condyloma, compared with 3 of 1,397 who received Gardasil, for an efficacy of 89%. Efficacy against PIN 1/2/3 was 100%, but the numbers were small (3 vs. 0 cases).
Efficacy against persistent infectiondefined as two or more consecutive positive samples with the same HPV strain 6 months apartwas 86% (101 placebo subjects vs. 15 who got Gardasil). The vaccine was highly immunogenic, with seroconversion rates at 7 months ranging from 97% for anti-HPV-18 antibodies to 99% for anti-HPV-6. At 24 months, seroconversion rates remained high for all strains except for anti-HPV-18, which dropped to 62%. However, efficacy remained high against all strains, he noted.
Adverse event rates did not differ significantly between groups. Injection site reactions were the most common adverse event. No serious vaccine-related adverse events were reported, and only two Gardasil and three placebo participants discontinued the study because of vaccine-related adverse events.
Because efficacy studies that include genital sampling and questions about sexual behavior are not feasible in sexually naive young adolescent boys, the FDA allowed Merck to use immunogenicity "bridging" data to represent vaccine efficacy in 9- to 15-year-old boys in order to gain approval for use in that age group.
Immune responses to each of the four vaccine strains were actually more than twice as high among 1,073 boys aged 9-15 years as they were among 2,025 boys 16-26 years old, while there were no significant differences in adverse events between the younger and older cohorts.
"We believe there is a real public health benefit to adding male vaccination to the already-recognized female vaccination," Dr. Haupt concluded.
'We believe there is a real … benefit to adding male vaccination to the already-recognized female vaccination.'
Source DR. HAUPT