9-Valent Human Papillomavirus Virus (HPV) Vaccine
9-Valent Human Papillomavirus Virus (HPV) Vaccine
The safety and efficacy of the 9-valent HPV vaccine were evaluated in five clinical trials prior to FDA approval. These studies, briefly described in the Gardasil® 9 prescribing information, include comparison studies with the quadrivalent HPV vaccine in women 16 to 26 years of age and studies in girls and boys 9–15 years of age to evaluate seroconversion and safety. Across all clinical trials, at least 99.5% of subjects became seropositive within one month of receiving their third dose. Maintenance of immune response has been established for up to 24 months after the initial dose of the vaccine, although more long-term antibody titer studies will be needed.
The results of a phase 2b-3 study evaluating the efficacy and immunogenicity of the 9-valent HPV vaccine were published in the February 19, 2015 issue of The New England Journal of Medicine. Joura and colleagues enrolled 14,215 women 16 to 26 years of age in their international randomized, double-blind comparison study. The subjects received either the 9-valent or quadrivalent vaccine in three doses, at day 1, month 2, and month 6. Cytologic testing was performed at baseline and at regular intervals throughout the study, ending at month 54 post-vaccination. Antibody titers were also evaluated after vaccination, and the titers for HPV types 6, 11, 16, and 18 were compared to ensure non-inferiority of the 9-valent vaccine to the quadrivalent vaccine.
The rate of high-grade cervical, vulvar, or vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0.1 per 1,000 person-years in the 9-valent vaccine group, compared to 1.6 per 1,000 person-years in the quadrivalent vaccine group, or 1 case versus 30 cases, resulting in an efficacy of the 9-valent vaccine of 96.7% (95% CI 80.9 to 99.8). Seroconversion was documented in nearly 100% of the patients in the 9-valent vaccine group within 1 month of their third dose. Antibody responses to HPV types 6, 11, 16, and 18 were not significantly different between the two groups. Injection site reactions (pain, swelling, erythema, or pruritus) were common in both groups, occurring in 90.7% of women given the 9-valent vaccine and 84.9% of those given the quadrivalent vaccine. Serious vaccine-related events were reported in only 2 patients in each group of more than 7,000 women.
The effect of concomitant administration with other vaccines was evaluated in a study of 1,237 adolescents given the 9-valent HPV with quadrivalent meningococcal conjugate vaccine and tetanus, diphtheria, acellular pertussis (Tdap) vaccine or at separate visits. Rates of seroconversion, evaluated one month post-dose, were similar between the two groups for each of the three vaccines. The incidence of injection site reactions was similar in the two groups, with the exception of a higher rate of swelling at the injection site in the concomitant administration group (14.4%) compared to the non-concomitant group (9.4%). The majority of the reactions were rated as mild to moderate in severity.
Clinical Trials
The safety and efficacy of the 9-valent HPV vaccine were evaluated in five clinical trials prior to FDA approval. These studies, briefly described in the Gardasil® 9 prescribing information, include comparison studies with the quadrivalent HPV vaccine in women 16 to 26 years of age and studies in girls and boys 9–15 years of age to evaluate seroconversion and safety. Across all clinical trials, at least 99.5% of subjects became seropositive within one month of receiving their third dose. Maintenance of immune response has been established for up to 24 months after the initial dose of the vaccine, although more long-term antibody titer studies will be needed.
The results of a phase 2b-3 study evaluating the efficacy and immunogenicity of the 9-valent HPV vaccine were published in the February 19, 2015 issue of The New England Journal of Medicine. Joura and colleagues enrolled 14,215 women 16 to 26 years of age in their international randomized, double-blind comparison study. The subjects received either the 9-valent or quadrivalent vaccine in three doses, at day 1, month 2, and month 6. Cytologic testing was performed at baseline and at regular intervals throughout the study, ending at month 54 post-vaccination. Antibody titers were also evaluated after vaccination, and the titers for HPV types 6, 11, 16, and 18 were compared to ensure non-inferiority of the 9-valent vaccine to the quadrivalent vaccine.
The rate of high-grade cervical, vulvar, or vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0.1 per 1,000 person-years in the 9-valent vaccine group, compared to 1.6 per 1,000 person-years in the quadrivalent vaccine group, or 1 case versus 30 cases, resulting in an efficacy of the 9-valent vaccine of 96.7% (95% CI 80.9 to 99.8). Seroconversion was documented in nearly 100% of the patients in the 9-valent vaccine group within 1 month of their third dose. Antibody responses to HPV types 6, 11, 16, and 18 were not significantly different between the two groups. Injection site reactions (pain, swelling, erythema, or pruritus) were common in both groups, occurring in 90.7% of women given the 9-valent vaccine and 84.9% of those given the quadrivalent vaccine. Serious vaccine-related events were reported in only 2 patients in each group of more than 7,000 women.
The effect of concomitant administration with other vaccines was evaluated in a study of 1,237 adolescents given the 9-valent HPV with quadrivalent meningococcal conjugate vaccine and tetanus, diphtheria, acellular pertussis (Tdap) vaccine or at separate visits. Rates of seroconversion, evaluated one month post-dose, were similar between the two groups for each of the three vaccines. The incidence of injection site reactions was similar in the two groups, with the exception of a higher rate of swelling at the injection site in the concomitant administration group (14.4%) compared to the non-concomitant group (9.4%). The majority of the reactions were rated as mild to moderate in severity.
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