Gardasil, Merck's Cervical Cancer Vaccine, Demonstrated Efficacy in Preventing HPV-Related Disease in Males in Phase III Study
Pivotal Study Evaluating Efficacy of GARDASIL in Males in Preventing HPV 6, 11, 16 and 18-Related External Genital Lesions
WHITEHOUSE STATION, N.J., Nov. 13, 2008 - GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant], the cervical cancer vaccine from Merck & Co., Inc., prevented 90 percent of external genital lesions caused by human papillomavirus (HPV) types 6, 11, 16 and 18 in a pivotal Phase III study in men aged 16 to 26. These are the only data evaluating efficacy of any HPV vaccine in preventing disease in males, and were presented for the first time this week at the European Research Organization on Genital Infection and Neoplasia (EUROGIN) International Multidisciplinary Conference.
The initial planned analysis of this study, an analysis of male study participants aged 16 to 26 who had not been infected with at least one of the four HPV types before the start of the study through one month after receiving their third dose of the vaccine or placebo, has been completed. This analysis was predetermined in the study protocol to be conducted after at least 32 cases of external genital lesions were observed. The study is ongoing, and additional data will be submitted to global regulatory agencies once available.
Merck remains on track to submit a supplemental Biologics License Application for GARDASIL to the U.S. Food and Drug Administration by the end of 2008 for the use of GARDASIL in boys and men ages 9 to 26 for the prevention of external genital lesions caused by HPV types 6, 11, 16 and 18. Other regulatory submissions around the world will occur as planned.
GARDASIL is not currently approved for males in the United States. GARDASIL is 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.
GARDASIL Reduced External Genital Lesions in Males by 90 Percent
The placebo-controlled, Phase III study was designed to determine the efficacy of GARDASIL in males against HPV 6, 11, 16, and 18-related external genital lesions, a composite endpoint that included: 1) genital warts (condylomata), 2) penile/perineal/perianal intraepithelial neoplasia (or PIN; PIN 2/3 can be pre-cursors to cancer) and 3) penile/perineal/perianal cancer. Penile/perineal/perianal is defined as related to or affecting the penis (penile), the area between the anus and the scrotum (perineal), or the opening of the rectum to the outside of the body (perianal).
The study evaluated approximately 3,400 heterosexual males 16 through 23 years of age and approximately 600 men 16 to 26 years of age who have sex with men. Participants were randomized in a 1-to-1 ratio to receive either GARDASIL or placebo at day one, two months and six months, with 36 months of planned follow-up from day one. At the time of vaccination, participants had no evidence of genital lesions, no history of genital warts and five or fewer lifetime sexual partners.
In the study, GARDASIL was 90.4 percent effective at reducing external genital lesions (3 cases in the vaccine group vs. 31 cases in placebo group; 95 percent CI: 69.2, 98.1, p-value <0.001). The three cases seen among those vaccinated with GARDASIL were cases of genital warts, resulting in GARDASIL being 89.4 percent effective in preventing genital warts (95 percent CI: 65.5, 97.9). For penile/perineal/perianal intraepithelial neoplasia or PIN, there were no cases in the vaccine group vs. 3 cases of PIN 1 or PIN 2/3 in the placebo group. There were no cases of penile/perineal/perianal cancer in either vaccine or placebo group. At the time of this analysis, the study had a mean duration of about 29 months.
No vaccine-related serious adverse events were reported in this study. A slightly higher proportion of study participants reported injection-site adverse events in the vaccine group compared to placebo (60.1 percent vs. 53.7 percent).
GARDASIL Also Achieved Statistical Significance on Both Secondary Endpoints
Two secondary endpoints also were evaluated in this pivotal study and results from these analyses were presented at EUROGIN. GARDASIL was 85.6 percent effective at reducing persistent infection (15 cases in the vaccine group vs. 101 cases in the placebo group; 95 percent CI: 75.1, 92.2, p-value <0.001). Persistent infection is when the same HPV type is detected through swabs or biopsies over two or more consecutive visits six months apart. In addition, GARDASIL was 44.7 percent effective at reducing "anytime" HPV DNA detection (136 cases in the vaccine group vs. 241 cases in the placebo group; 95 percent CI: 31.5, 55.6, p-value <0.001). "Anytime" HPV DNA detection means HPV DNA is found through swabs or biopsies at any visit; persistent infection is a part of "anytime" HPV DNA detection.
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.
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.
The most common adverse reaction was headache. Common adverse reactions that were observed among recipients of GARDASIL at a frequency of at least 1.0 percent and greater than placebo were fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus, and bruising.
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.
Human Papillomavirus: A Virus that Affects Both Men and Women
According to the Centers for Disease Control and Prevention, in the U.S. alone, an estimated 20 million men and women are currently infected with HPV, and another 6.2 million people become newly infected each year. For most, HPV goes away on its own. However, certain low-risk types of HPV can cause external genital lesions. More than one million cases of external genital lesions in men and women occur each year in the U.S. and more than 30 million occur each year worldwide. In addition for women, certain high-risk types of HPV, if unrecognized and untreated, can lead to cervical cancer.
HPV is a virus that can infect the genital region of men and women. There are an estimated 30 to 40 types of genital HPV. HPV transmission can happen with any kind of intimate genital contact with someone who has HPV; sexual intercourse is not needed. Most sexually active people will have HPV at some time in their lives.
Other Information about GARDASIL
In 1995, Merck entered into a license agreement and research collaboration with CSL Limited of Australia relating to technology used in GARDASIL. GARDASIL also is the subject of other third-party licensing agreements.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com [1].
Forward-Looking Statement
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 Dec. 31, 2007, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
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