Efficacy of GARDASIL 9

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

Efficacy of GARDASIL 9

High Efficacy in Clinical Studies in Patients 16-26 Years of Age

Efficacy of GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] was assessed in 5 AAHS-controlled clinical studies of persons 16-26 years of age:

Effectiveness of GARDASIL 9 in the PPE population against persistent infection and the incidence of certain cancers and diseases caused by HPV Types 6, 11, 16, and 18 was inferred from a noninferiority comparison of GMTs versus GARDASIL.

~98%

CERVICAL CANCER
HPV 16- or 18-related CIN 2/3 or AIS

n=8493

100%

VULVAR CANCER
HPV 16- or 18-related VIN 2/3

n=7772

100%

VAGINAL CANCER
HPV 16- or 18-related VaIN 2/3

n=7772

~75%

ANAL CANCER
HPV 6-, 11-, 16-, or 18-related AIN 2/3

n=194

Efficacy and effectiveness of GARDASIL are relevant to GARDASIL 9 since the vaccines are manufactured similarly and contain 4 of the same HPV L1 VLPs.

Abbreviations: AAHS, amorphous aluminum hydroxyphosphate sulfate; AIN, anal intraepithelial neoplasia; AIS, adenocarcinoma in situ; CIN, cervical intraepithelial neoplasia; GMT, geometric mean titers; PPE, per-protocol efficacy; VaIN, vaginal intraepithelial neoplasia; VIN, vulvar intraepithelial neoplasia; VLP, virus-like particle.

GARDASIL 9 study efficacy against cancers caused by HPV Types 31, 33, 45, 52, and 58 in females 16-26 years of age

~97%

VULVAR, VAGINAL, AND CERVICAL
CANCER, HPV 31-, 33-, 45-, 52-, 58-
RELATED CIN 2/3, AIS, CERVICAL
CANCER, VIN 2/3, VaIN 2/3, VULVAR
CANCER, AND VAGINAL CANCER
HPV 31-, 33-, 45-, 52-, and 58-related

n=6016

One case in the group receiving GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) (n=6016) vs 30 cases in the group receiving GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=6017) (95% CI, 80.9%, 99.8%).

Abbreviations: AIN, anal intraepithelial neoplasia; AIS, adenocarcinoma in situ; CIN, cervical intraepithelial neoplasia; VaIN, vaginal intraepithelial neoplasia; VIN, vulvar intraepithelial neoplasia.

Demonstrated Efficacy in Adults 27-45 Years of Age

GARDASIL efficacy in women in the PPE population, in preventing HPV 6-, 11-, 16-, and 18-related:

~88%

GENITAL WARTS, VIN, VaIN, VULVAR
CANCER, VAGINAL CANCER, CERVICAL
DYSPLASIA (ANY GRADE CIN), AIS, AND
CERVICAL CANCER
HPV 6-, 11-, 16-, and 18-related
n=3253

~95%

GENITAL WARTS, CERVICAL DYSPLASIA
HPV 6-, 11-, 16-, and 18-related



n=3253

In men 27 to 45 years of age, efficacy is inferred from efficacy data in women 27 to 45 years of age, and supported by immunogenicity data.

Efficacy and effectiveness of GARDASIL are relevant to GARDASIL 9 since the vaccines are manufactured similarly and contain 4 of the same HPV L1 VLPs.

Efficacy in men is inferred from efficacy data in women and supported by immunogenicity data.

studyDesignEff1

Study Design

GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Study Design

Efficacy of GARDASIL was assessed in 5 AAHS-controlled, double-blind, randomized clinical studies evaluating 24,596 individuals in the PPE population (20,541 girls and women 16 to 26 years of age and 4055 boys and men 16 to 26 years of age). Subjects received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month post-dose 3 (Month 7).

GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Study Results

Cervical: 2 HPV 16- or 18-related CIN 2/3 or AIS cases in the group receiving GARDASIL (n=8493) vs 112 cases in the group receiving placebo (n=8464) [95% CI, 93.5-99.8];

Vulvar/Vaginal: No HPV 16- or 18-related VIN 2/3 or VaIN 2/3 cases in either group receiving GARDASIL (n=7772) vs 10 cases in the VIN 2/3 group receiving placebo (n=7744) [95% CI, 55.5-100.0], and 9 cases in the VaIN 2/3 group receiving placebo (n=7744) [95% CI, 49.5-100.0]; Anal: 3 (HPV Types 6-, 11-, 16-, or 18-related) AIN 2/3 cases in the male group receiving GARDASIL (n=194) vs 13 cases in the male group receiving placebo (n=208) [95% CI, 8.8-95.4];

Genital Warts: 3 HPV 6-, 11-, 16-, or 18-related genital warts cases in the male group receiving GARDASIL (n=1394) vs 28 genital warts cases in the male group receiving placebo (n=1404) [95% CI, 65.3-97.9]; External Genital Lesions (males): 3 cases HPV Types 6-, 11-, 16-, or 18-related external genital lesions in the group receiving GARDASIL (n =1394) vs 32 cases of eternal genital lesions in the group receiving placebo (n=1404) [95% CI, 70.1-98.2]; External Genital Lesions (females): 2 HPV 6-, 11-, 16-, or 18-related genital warts cases in the group receiving GARDASIL (n=7900) vs 193 cases in the group receiving placebo (n=7902) [95% CI, 96.2-99.9].

GARDASIL®9  [Human Papillomavirus 9-valent Vaccine, Recombinant] Study Design

Efficacy of GARDASIL 9 in 16‐ through 26‐year‐old girls and women was assessed in an active comparator-controlled, double‐blind, randomized clinical study that included a total of 14, 204 women (GARDASIL 9=7099; GARDASIL=7105) who were enrolled and vaccinated without prescreening for the presence of HPV infection. Subjects were followed up with a median duration of 40 months (range 0 to 64 months) after the last vaccination and efficacy of all endpoints was measured starting after the Month 7 visit. Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) (Types 31, 33, 45, 52, and 58) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month post‐dose 3 (Month 7).

GARDASIL®9 [Human Papillomavirus 9-valent Vaccine, Recombinant] Study Results

One HPV 31-, 33-, 45-, 52-, and 58-related case (CIN 2/3, AIS, Cervical Cancer, VIN 2/3, VaIN 2/3, Vulvar Cancer, and Vaginal Cancer) in the group receiving GARDASIL 9 (n=6016) vs 30 cases in the group receiving GARDASIL (n=6017) [95% CI, 80.9‐99.8].

AAHS, amorphous aluminum hydroxyphosphate sulfate; PCR, polymerase chain reaction.

studyDesignEff2

Study Design

GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Study Design

A clinical trial evaluated efficacy of GARDASIL in 3,253 women 27 through 45 years of age, based on a combined endpoint of HPV 6-, 11-, 16-, or 18-related persistent infection, genital warts, vulvar and vaginal dysplastic lesions of any grade, CIN of any grade, AIS, and cervical cancer. These women were randomized 1:1 to receive either GARDASIL or AAHS control. The PPE population received all 3 vaccinations within 1 year of enrollment, did not have major deviations from the study protocol, were naïve (PCR negative and seronegative) to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1 and remained PCR negative to the relevant HPV type(s) through 1 month post-dose 3 (Month 7). The clinical trial was conducted in 2 phases: a base study and a long-term study extension.

GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Study Results

In the base study (median duration of follow-up of 3.5 years post-dose 3), the efficacy of GARDASIL against the combined incidence of HPV 6-, 11-, 16-, and 18-related persistent  infection, genital warts, VIN, VaIN, vulvar cancer, vaginal cancer, cervical dysplasia (any grade CIN), AIS, and cervical cancer in the PPE population was 87.7% (95% CI, 75.4%, 94.6%). The efficacy estimate for the combined endpoint was driven primarily by prevention of persistent infection. The efficacy of GARDASIL against the combined incidence of HPV 6-, 11-, 16-, and 18-related genital warts or cervical dysplasia was 95.0% (95% CI, 68.7%, 99.9%) in the PPE population. While no statistically significant efficacy was demonstrated for GARDASIL in the base study for prevention of cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), adenocarcinoma in situ (AIS), or cervical cancer related to HPV Types 16 and 18, there was 1 case of CIN 2/3 observed in the GARDASIL group and 5 cases in the placebo group. The CIN 2 case in the GARDASIL group tested positive by PCR for HPV 16 and HPV 51.

In the long-term extension study, subjects from Colombia (n=600) randomized to the GARDASIL group in the base study were monitored for HPV 6-, 11-, 16-, and 18-related genital warts or cervical dysplasia. The median follow-up post-dose 3 was 8.9 years with a range of 0.1 to 10.1 years over total of 3,518 person-years. During the long-term extension phase, no cases of HPV 6-, 11-, 16-, or 18-related CIN (any grade) or genital warts were observed in the PPE population.

ref8

Reference

  1. Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68(32):698-702.
ref9

Reference

  1. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package US-GSL-01415.

ref23

Reference

  1. Saraiya M, Unger ER, Thompson TD, et al. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. JNCI J Natl Cancer Inst (2015) 107(6): 1-12. doi: 10.1093/jnci/djv086.

Indication for GARDASIL® 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

GARDASIL 9 does not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers as recommended by a health care provider.

GARDASIL 9 has not been demonstrated to provide protection against diseases caused by:

  • HPV types not covered by the vaccine
  • HPV types to which a person has previously been exposed through sexual activity

Not all vulvar, vaginal, anal, oropharyngeal and other head and neck cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

GARDASIL ®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity of GARDASIL 9 has not been established.

Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid or anterolateral area of the thigh.

  • For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6–12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
  • For individuals 15 through 45 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.

Before administering GARDASIL 9, please read the Prescribing Information. The Patient Information also is available.

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

GARDASIL 9 does not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers as recommended by a health care provider.

GARDASIL 9 has not been demonstrated to provide protection against diseases caused by:

  • HPV types not covered by the vaccine
  • HPV types to which a person has previously been exposed through sexual activity

Not all vulvar, vaginal, anal, oropharyngeal and other head and neck cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

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US-GSL-02513 10/20