Vaccine Information: GARDASIL (Page 4 of 8)

14.2 Prophylactic Efficacy – HPV Types 6, 11, 16, and 18 in Boys and Men 16 through 26 Years of Age

The primary analyses of efficacy were conducted in the per-protocol efficacy (PPE) population. This population consisted of boys and men who received all 3 vaccinations within 1 year of enrollment, did not have major deviations from the study protocol, and were naïve (PCR negative and seronegative) to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1 and through 1 month postdose 3 (Month 7). Efficacy was measured starting after the Month 7 visit.

GARDASIL was efficacious in reducing the incidence of genital warts related to vaccine HPV types 6 and 11 in those boys and men who were PCR negative and seronegative at baseline (Table 12). Efficacy against penile/perineal/perianal intraepithelial neoplasia (PIN) grades 1/2/3 or penile/perineal/perianal cancer was not demonstrated as the number of cases was too limited to reach statistical significance.

Table 12: Analysis of Efficacy of GARDASIL in the PPE * Population of 16- Through 26-Year-Old Boys and Men for Vaccine HPV Types
Endpoint GARDASIL AAHS Control % Efficacy (95% CI)
N Number of cases N Number of cases
CI = Confidence Interval
AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate
*
The PPE population consisted of individuals who received all 3 vaccinations within 1 year of enrollment, did not have major deviations from the study protocol, and were naïve (PCR negative and seronegative) to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1 and through 1 month postdose 3 (Month 7).
N = Number of individuals with at least 1 follow-up visit after Month 7
External Genital Lesions HPV 6-, 11-, 16-, or 18- related
External Genital Lesions 1394 3 1404 32 90.6 (70.1, 98.2)
Condyloma 1394 3 1404 28 89.3 (65.3, 97.9)
PIN 1/2/3 1394 0 1404 4 100.0 (-52.1, 100.0)

14.3 Prophylactic Efficacy – Anal Disease Caused by HPV Types 6, 11, 16, and 18 in Boys and Men 16 through 26 Years of Age in the MSM Sub-study

A sub-study of Study 5 evaluated the efficacy of GARDASIL against anal disease (anal intraepithelial neoplasia and anal cancer) in a population of 598 MSM. The primary analyses of efficacy were conducted in the per-protocol efficacy (PPE) population of Study 5.

GARDASIL was efficacious in reducing the incidence of anal intraepithelial neoplasia (AIN) grades 1 (both condyloma and non-acuminate), 2, and 3 related to vaccine HPV types 6, 11, 16, and 18 in those boys and men who were PCR negative and seronegative at baseline (Table 13).

Table 13: Analysis of Efficacy of GARDASIL for Anal Disease in the PPE * Population of 16- Through 26-Year-Old Boys and Men in the MSM Sub-study for Vaccine HPV Types
HPV 6-, 11-, 16-, or 18- related Endpoint GARDASIL AAHS Control % Efficacy (95% CI)
N Number of cases N Number of cases
CI = Confidence Interval
AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate
*
The PPE population consisted of individuals who received all 3 vaccinations within 1 year of enrollment, did not have major deviations from the study protocol, and were naïve (PCR negative and seronegative) to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1 and through 1 month postdose 3 (month 7).
N = Number of individuals with at least 1 follow-up visit after Month 7
AIN 1/2/3 194 5 208 24 77.5 (39.6, 93.3)
AIN 2/3 194 3 208 13 74.9 (8.8, 95.4)
AIN 1 194 4 208 16 73.0 (16.3, 93.4)
Condyloma Acuminatum 194 0 208 6 100.0 (8.2, 100.0)
Non-acuminate 194 4 208 11 60.4 (-33.5, 90.8)

14.4 Population Impact in Girls and Women 16 through 26 Years of Age

Effectiveness of GARDASIL in Prevention of HPV Types 6-, 11-, 16-, or 18-Related Genital Disease in Girls and Women 16 Through 26 Years of Age, Regardless of Current or Prior Exposure to Vaccine HPV Types

The clinical trials included girls and women regardless of current or prior exposure to vaccine HPV types, and additional analyses were conducted to evaluate the impact of GARDASIL with respect to HPV 6-, 11-, 16-, and 18-related cervical and genital disease in these girls and women. Here, analyses included events arising among girls and women regardless of baseline PCR status and serostatus, including HPV infections that were present at the start of vaccination as well as events that arose from infections that were acquired after the start of vaccination.

The impact of GARDASIL in girls and women regardless of current or prior exposure to a vaccine HPV type is shown in Table 14. Impact was measured starting 1 month Postdose 1. Prophylactic efficacy denotes the vaccine’s efficacy in girls and women who are naïve (PCR negative and seronegative) to the relevant HPV types at Day 1. Vaccine impact in girls and women who were positive for vaccine HPV infection, as well as vaccine impact among girls and women regardless of baseline vaccine HPV PCR status and serostatus are also presented. The majority of CIN and genital warts, VIN, and VaIN related to a vaccine HPV type detected in the group that received GARDASIL occurred as a consequence of HPV infection with the relevant HPV type that was already present at Day 1.

There was no clear evidence of protection from disease caused by HPV types for which girls and women were PCR positive regardless of serostatus at baseline.

Table 14: Effectiveness of GARDASIL in Prevention of HPV 6, 11, 16, or 18-Related Genital Disease in Girls and Women 16 Through 26 Years of Age, Regardless of Current or Prior Exposure to Vaccine HPV Types
Endpoint Analysis GARDASIL or HPV 16 L1 VLP Vaccine AAHS Control % Reduction(95% CI)
N Cases N Cases
CI = Confidence Interval
N = Number of individuals who have at least one follow-up visit after Day 1
Note 1: The 16- and 18-related CIN 2/3 or AIS composite endpoint included data from studies 1, 2, 3, and 4. All other endpoints only included data from studies 2, 3, and 4.
Note 2: Positive status at Day 1 denotes PCR positive and/or seropositive for the respective type at Day 1.
Note 3: Table 14 does not include disease due to non-vaccine HPV types.
AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate
*
Includes all individuals who received at least 1 vaccination and who were HPV-naïve (i.e., seronegative and PCR negative) at Day 1 to the vaccine HPV type being analyzed. Case counting started at 1 month postdose 1.
Includes all individuals who received at least 1 vaccination and who were HPV positive or had unknown HPV status at Day 1, to at least one vaccine HPV type. Case counting started at Day 1.
Out of the 148 AAHS control cases of 16/18 CIN 2/3, 2 women were missing serology or PCR results for Day 1.
§
There is no expected efficacy since GARDASIL has not been demonstrated to provide protection against disease from vaccine HPV types to which a person has previously been exposed through sexual activity.
Includes all individuals who received at least 1 vaccination (regardless of baseline HPV status at Day 1). Case counting started at 1 month postdose 1.
#
Includes 2 AAHS control women with missing serology/PCR data at Day 1.
Þ
Includes 1 woman with missing serology/PCR data at Day 1.
HPV 16- or 18-related CIN 2/3 or AIS Prophylactic Efficacy * 9346 4 9407 155 97.4 (93.3, 99.3)
HPV 16 and/or HPV 18 Positive at Day 1 2870 142 2898 148 §
Girls and Women Regardless of Current or Prior Exposure to HPV 16 or 18 9836 146 9904 303 51.8 (41.1, 60.7)
HPV 16- or 18-related VIN 2/3 or VaIN 2/3 Prophylactic Efficacy * 8642 1 8673 34 97.0 (82.4, 99.9)
HPV 16 and/or HPV 18 Positive at Day 1 1880 8 1876 4 §
Girls and Women Regardless of Current or Prior Exposure to HPV 16 or 18 8955 9 8968 38 76.3 (50.0, 89.9)
HPV 6-, 11-, 16-, 18-related CIN (CIN 1, CIN 2/3) or AIS Prophylactic Efficacy * 8630 16 8680 309 94.8 (91.5, 97.1)
HPV 6, HPV 11, HPV 16, and/or HPV 18 Positive at Day 1 2466 186# 2437 213# §
Girls and Women Regardless of Current or Prior Exposure to Vaccine HPV Types 8819 202 8854 522 61.5 (54.6, 67.4)
HPV 6-, 11-, 16-, or 18-related Genital Warts Prophylactic Efficacy * 8761 10 8792 252 96.0 (92.6, 98.1)
HPV 6, HPV 11, HPV 16, and/or HPV 18 Positive at Day 1 2501 51Þ 2475 55 Þ §
Girls and Women Regardless of Current or Prior Exposure to Vaccine HPV Types 8955 61 8968 307 80.3 (73.9, 85.3)
HPV 6- or 11-related Genital Warts Prophylactic Efficacy * 7769 9 7792 246 96.4 (93.0, 98.4)
HPV 6 and/or HPV 11 Positive at Day 1 1186 51 1176 54 §
Girls and Women Regardless of Current or Prior Exposure to Vaccine HPV Types 8955 60 8968 300 80.1 (73.7, 85.2)

Effectiveness of GARDASIL in Prevention of Any HPV Type Related Genital Disease in Girls and Women 16 Through 26 Years of Age, Regardless of Current or Prior Infection with Vaccine or Non-Vaccine HPV Types

The impact of GARDASIL against the overall burden of dysplastic or papillomatous cervical, vulvar, and vaginal disease regardless of HPV detection, results from a combination of prophylactic efficacy against vaccine HPV types, disease contribution from vaccine HPV types present at time of vaccination, the disease contribution from HPV types not contained in the vaccine, and disease in which HPV was not detected.

Additional efficacy analyses were conducted in 2 populations: (1) a generally HPV-naïve population (negative to 14 common HPV types and had a Pap test that was negative for SIL [Squamous Intraepithelial Lesion] at Day 1), approximating a population of sexually-naïve girls and women and (2) the general study population of girls and women regardless of baseline HPV status, some of whom had HPV-related disease at Day 1.

Among generally HPV-naïve girls and women and among all girls and women in the study population (including girls and women with HPV infection at Day 1), GARDASIL reduced the overall incidence of CIN 2/3 or AIS; of VIN 2/3 or VaIN 2/3; of CIN (any grade) or AIS; and of Genital Warts (Table 15). These reductions were primarily due to reductions in lesions caused by HPV types 6, 11, 16, and 18 in girls and women naïve (seronegative and PCR negative) for the specific relevant vaccine HPV type. Infected girls and women may already have CIN 2/3 or AIS at Day 1 and some will develop CIN 2/3 or AIS during follow-up, either related to a vaccine or non-vaccine HPV type present at the time of vaccination or related to a non-vaccine HPV type not present at the time of vaccination.

Table 15: Effectiveness of GARDASIL in Prevention of Any HPV Type Related Genital Disease in Girls and Women 16 Through 26 Years of Age, Regardless of Current or Prior Infection with Vaccine or Non-Vaccine HPV Types
Endpoints Caused by Vaccine or Non-vaccine HPV Types Analysis GARDASIL AAHS Control % Reduction(95% CI)
N Cases N Cases
CI = Confidence Interval
AAHS Control = Amorphous Aluminum Hydroxyphosphate Sulfate
*
Includes all individuals who received at least 1 vaccination and who had a Pap test that was negative for SIL [Squamous Intraepithelial Lesion] at Day 1 and were naïve to 14 common HPV types at Day 1. Case counting started at 1 month postdose 1.
Includes all individuals who received at least 1 vaccination (regardless of baseline HPV status or Pap test result at Day 1). Case counting started at 1 month postdose 1.
CIN 2/3 or AIS Prophylactic Efficacy * 4616 77 4680 136 42.7 (23.7, 57.3)
Girls and Women Regardless of Current or Prior Exposure to Vaccine or Non-Vaccine HPV Types 8559 421 8592 516 18.4 (7.0, 28.4)
VIN 2/3 and VaIN 2/3 Prophylactic Efficacy * 4688 7 4735 31 77.1 (47.1, 91.5)
Girls and Women Regardless of Current or Prior Exposure to Vaccine or Non-Vaccine HPV Types 8688 30 8701 61 50.7 (22.5, 69.3)
CIN (Any Grade) or AIS Prophylactic Efficacy * 4616 272 4680 390 29.7 (17.7, 40.0)
Girls and Women Regardless of Current or Prior Exposure to Vaccine or Non-Vaccine HPV Types 8559 967 8592 1189 19.1 (11.9, 25.8)
Genital Warts Prophylactic Efficacy * 4688 29 4735 169 82.8 (74.3, 88.8)
Girls and Women Regardless of Current or Prior Exposure to Vaccine or Non-Vaccine HPV Types 8688 132 8701 350 62.5 (54.0, 69.5)

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