Data on the Use of GARDASIL in Men
Presented at the 25th Annual International Papillomavirus Conference
At the International Papillomavirus Conference in May 2009, Merck presented interim results from studies that assessed the use of GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant] both in heterosexual men (HM) and men who have sex in men (MSM); and evaluated the immune response produced in males.
Following are details of these studies:
Efficacy against HPV-related Genital Disease and Infection in Young Men1
· The randomized, double-blind, placebo-controlled trial study was designed to examine the efficacy of GARDASIL in 4,065 men aged 16 to 26 years against HPV 6/11/16/18-related external genital lesions and infection. External genital lesions include: external genital warts, penile/perineal/perianal intraepithelial neoplasia (PIN), and penile/perineal/perianal cancer. The study included both HM and MSM.
· Study participants included men who were naïve to the relevant HPV type at the start of the study and through month seven (one month after completion of the three-dose series). All three doses did not deviate from the study, and endpoints were counted starting after month seven (Per Protocol Efficacy Population [PPE]). The results included:
· 90.4 percent efficacy (95 percent CI: 69.2, 98.1) against any HPV 6/11/16/18-related external genital lesion.
· 89.4 percent efficacy (95 percent CI: 65.5, 97.9) against condyloma and 100 percent against PIN (95 percent CI: <0, 100).
· 85.6 percent efficacy (97.5 percent CI: 73.4, 92.9) against HPV 6/11/16/18 persistent infection. Persistent infection is when the same HPV type is detected through swabs or biopsies over two or more consecutive visits six months apart.
· 44.7 percent efficacy (95 percent CI: 31.5, 55.6) against DNA detection at one or more visits
Efficacy against HPV 6/11/16/18-related Genital Disease in MSM2
· The randomized, placebo-controlled study was designed to evaluate the effectiveness of GARDASIL in 602 MSM aged 16 to 26 years against HPV 6/11/16/18-related external genital lesions as well as anogenital persistent infection, DNA detection, and immunogenicity. This was the PPE population with median follow up of one year.
· The results included:
· 94.4 percent efficacy (95 percent CI: 64.4, 99.9), against HPV 6/11/16/18 persistent infection.
· 79 percent efficacy (95 percent CI: <0, 99.6) against HPV 6/11/16/18-related external genital lesions.
· 96.5 percent, 97.4 percent, 94.2 percent, and 89.5 percent of MSM receiving GARDASIL produced antibodies against HPV 6, 11, 16, and 18, respectively, by the study’s seventh month.
· 83.9 percent, 96.4 percent, 100 percent, and 55.7 percent of MSM receiving GARDASIL produced antibodies against HPV 6, 11, 16 and 18, respectively, by the month 24 of the study.
· 48.8 percent efficacy (95 percent CI 11.6, 71.2) at any visit (21 vaccines cases versus 42 placebo cases).
Immune Response to GARDASIL in Young Men3
· This randomized, double-blind, placebo-controlled trial was designed to evaluate the ability of GARDASIL to generate antibodies against HPV 6/11/16/18 as measured by the Merck cLIA in 4065 HM and MSM aged 16 to 26 years of age.
· The ability of GARDASIL to produce an immune response in men was shown to be non-inferior to the immune response demonstrated in women. The findings show that by month seven the following proportion of subjects developed antibodies against HPV 6: 98.9 percent; HPV 11: 99.2 percent; HPV 16: 98.8 percent; and HPV 18: 97.4 percent.
Natural History of HPV 6/11/16/18 Infections in Young Men
· The study was designed to examine the clearance, persistence and progression of incident external genital HPV 6/11/16/18 infections in 2,038 HM and MSM aged 15 to 27 years who participated in the placebo arm of a GARDASIL clinical trial. They were followed for up to three years.
· The study found MSM were more likely to develop genital warts following incident external genital HPV 6/11 infections than HM. The findings show that 40.7 percent of MSM and 22.7 percent of HM (p < .05) were estimated to develop genital warts positive for HPV 6 or 11 within 12 months following external genital HPV 6 or 11 infections (n = 154).
GARDASIL is currently indicated for use in girls and young women 9 through 26 years of age for the prevention of cervical, vulvar and vaginal cancers caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18.
Additional Important Information about GARDASIL
GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.
The health care provider should inform the patient, parent or guardian that vaccination does not substitute for routine cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care.
GARDASIL is not recommended for use in pregnant women.
Vaccination with GARDASIL may not result in protection in all vaccine recipients. GARDASIL is not intended to be used for treatment of active genital warts, cervical, vaginal and vulvar cancers, cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN) or vaginal intraepithelial neoplasia (VaIN).
GARDASIL has not been demonstrated to provide protection against disease from vaccine and non-vaccine HPV types to which a woman has previously been exposed through sexual activity. GARDASIL has not been shown to protect against diseases due to HPV types not contained in the vaccine.
Not all vulvar and vaginal cancers are caused by human papillomavirus (HPV), and GARDASIL protects only against those vulvar and vaginal cancers caused by HPV types 16 and 18.
In clinical studies for GARDASIL, headache was the most commonly reported adverse reaction with near equal frequency in the GARDASIL and control group (28.2 percent vs. 28.4 percent). Vaccine-related adverse reactions that were observed at a frequency of at least 1.0 percent among recipients of GARDASIL and also greater than those observed among control group, respectively, were pain (83.9 percent vs. 75.4 percent), swelling (25.4 percent vs. 15.8 percent), erythema (24.7 percent vs. 18.4 percent), fever (13.0 percent vs. 11.2 percent), nausea (6.7 percent vs. 6.5 percent), pruritis (3.2 percent vs. 2.8 percent), dizziness (4.0 percent vs. 3.7 percent) and bruising (2.8 percent vs. 3.2 percent).
In addition, syncope has been reported following vaccination with GARDASIL, sometimes resulting in falling with injury. Observation for 15 minutes after administration is recommended.
Dosage and Administration for GARDASIL
GARDASIL is a ready-to-use, three-dose, intramuscular vaccine. GARDASIL should be administered in three separate intramuscular injections in the deltoid region of the upper arm or in the higher anterolateral area of the thigh. The following dosage schedule is recommended: first dose at elected date, second dose two months after the first dose and the third dose six months after the first dose.
GARDASIL is Approved in 109 Countries
GARDASIL (sold in some countries as SILGARD®) has been approved in 109 countries, and additional applications are currently under review with regulatory agencies in many more countries around the world.
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This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended December 31, 2008, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.
Prescribing Information and Patient Product Information for GARDASIL® are attached and is also available at www.gardasil.com.
GARDASIL® is a registered trademark of Merck & Co. Inc., Whitehouse Station, N.J., USA