On June 8,
2006, the U.S. Food and Drug Administration
approved Quadrivalent Human Papillomavirus
(Types 6, 11, 16, 18) Recombinant Vaccine (Gardasil,
Merck & Co., Inc.) for vaccination of females
9 to 26 years of age for prevention of the
following diseases caused by Human
Papillomavirus (HPV) Types 6, 11, 16, and 18:
- Cervical
cancer
- Genital
warts (condyloma acuminata)
- The
following precancerous or dysplastic
lesions:
- Cervical
adenocarcinoma in situ (AIS)
- Cervical
intraepithelial neoplasia (CIN) grade 2
and grade 3
- Vulvar
intraepithelial neoplasia (VIN) grade 2
and grade 3
- Vaginal
intraepithelial neoplasia (VaIN) grade 2
and grade 3
- Cervical
intraepithelial neoplasia (CIN) grade 1
This vaccine is
not intended to be used for treatment of
cervical cancer, CIN, VIN, VaIN, or genital
warts.
Gardasil has not been shown to protect against
diseases due to non-vaccine HPV types.
Vaccination does not substitute for routine
cervical cancer screening. Gardasil recipients
should continue to undergo cervical cancer
screening per standard of care.
The efficacy of the vaccine was studied in
four randomized, double-blind,
placebo-controlled trials enrolling a total of
20,541 females between the ages of 16 and 26.
Subjects were randomized to receive three
doses of the vaccine (on a schedule of 0, 2,
and 6 months) or placebo. The per-protocol
population consisted of individuals who
received all 3 vaccinations within 1 year of
enrollment who did not have major deviations
from the study protocol and were naïve to the
relevant HPV type(s) prior to dose 1 and
through 1 month Postdose 3. In the
per-protocol population, the efficacy of the
vaccine was:
- 100% (95%
CI: 92.9%, 100%) for prevention of HPV 16-
or 18- related CIN 2/3 or AIS;
- 95.2% (95%
CI: 87.2%, 98.7%) for prevention of HPV 6-,
11-, 16-, or 18- related CIN or AIS;
- 100% (95%
CI: 55.5%, 100.0%) for prevention of HPV 16-
or 18-related VIN 2/3 or VaIN 2/3; and
- 98.9% (95%
CI: 93.7%, 100.0%) for prevention of HPV 6-,
11-, 16-, or 18- related genital warts.
There was no
clear evidence of protection from disease
caused by HPV types for which subjects were
PCR positive (cervicovaginal specimen) and/or
seropositive at baseline. Individuals who were
already infected with 1 or more
vaccine-related HPV types prior to vaccination
were protected from clinical disease caused by
the remaining vaccine HPV types.
In the general study population, i.e., females
with any HPV status at baseline who received
at least one vaccine dose with case counting
started at 1 month Postdose 1, the
prophylactic efficacy of the vaccine was:
- 39.0% (95%
CI: 23.3%, 51.7%) for prevention of HPV 16-
or 18- related CIN 2/3 or AIS;
- 46.4% (95%
CI: 35.2%, 55.7%) for prevention of HPV 6-,
11-, 16-, or 18- related CIN and AIS;
- 9.1% (95%
CI: 29.8%, 87.9%) for prevention of HPV 16-
or 18-related VIN 2/3 and VaIN 2/3; and
- 68.5% (95%
CI: 57.5%, 77.0%) for prevention of HPV 6-,
11-, 16-, or 18- related genital warts.
Anti-HPV
antibody responses 1 month Postdose 3 among
9-15 year old girls were non-inferior to anti-HPV
responses in 16-26 year old females in the
combined database of immunogenicity studies
for Gardasil. On the basis of this
immunogenicity bridging, the efficacy of
Gardasil in 9-15 years old girls was inferred.
Administration of the vaccine with hepatitis B
vaccine did not affect the immunogenicity of
either vaccine, whether administered at the
same or different visits.
The most common vaccination site toxicities
observed for Gardasil compared to
aluminum-containing placebo and saline placebo
were pain (83.9% vs. 75.4% and 48.6%),
swelling (25.4% vs. 15.8% and 7.3%), and
erythema (24.6% vs. 18.4% and 12.1%). The most
common systemic adverse events for Gardasil
compared to saline placebo were fever (13.0%
vs. 11.2%) and nausea (6.7% vs. 6.6%).
Full prescribing information, including
clinical trial information, safety, dosing,
drug-drug interactions and contraindications
is available at
http://www.fda.gov/cber/label/hpvmer060806LB.pdf. For additional information on Gardasil, please see http://www.fda.gov/cber/products/hpvmer060806.htm
Healthcare professionals should report all
serious adverse events suspected to be
associated with the use of any medicine and
device to FDA’s MedWatch Reporting System by
phone at 1-800-FDA-1088; by facsimile
1-800-FDA-0178 by mail using the Form 3500 at
http://www.fda.gov/medwatch.index.html.
For further information related to oncology
drug approvals, regulatory information, and
other oncology resources, please refer to the
FDA “Oncology Tools” website at
www.fda.gov/cder/cancer.