Gardasil, The Cervical Cancer Vaccine Is Effective, Merck

Gardasil and Cervical Cancer

In investigational study, GARDASIL, Merck's cervical cancer vaccine, reduced incidence of HPV 6, 11, 16 and 18-related persistent infection and disease in women through age 45.

GARDASIL [Human Papillomavirus Quadrivalent] (Types 6, 11, 16, 18) Vaccine, Recombinant] prevented 91 percent of cases of persistent infection, low-grade cervical abnormalities, and pre-cancers, and external genital lesions caused by HPV types 6, 11, 16 and 18 compared with placebo in women aged 24 through 45, according to new data presented today at the 24th International Papillomavirus Conference (IPC) in Beijing, China.

The primary results evaluated women who were free of infection from at least one vaccine HPV type when they began the study, and who remained free of infection with the relevant HPV type(s) until they completed the three-dose vaccination regimen. GARDASIL is currently indicated for girls and women 9 through 26 years of age for the prevention of cervical cancer, precancerous or dysplastic lesions, and genital warts caused by HPV types 6, 11, 16 and 18.

"Women remain at significant risk for acquiring HPV infections and developing HPV-related diseases throughout their lifetime," said Eliav Barr M.D., executive director of Biologics Clinical Research and head of the HPV Vaccine Program, Merck Research Laboratories. "These data build on the clinical program for GARDASIL and will help us to understand the potential benefit that GARDASIL may have in women through age 45."

Merck will submit these data to the U.S. Food and Drug Administration (FDA) before the end of the year to seek an indication for women through age 45.

The international multi-center study, designed to examine if GARDASIL is effective at reducing disease and persistent infection caused by HPV types 6, 11, 16 and 18, involved more than 3,800 women. Women included in the study also had no history of: LEEP (loop electrosurgical excision procedure) or hysterectomy; biopsy-diagnosed cervical HPV disease in the past five years; or history of genital warts.

Because GARDASIL is designed to prevent HPV 6, 11, 16 and 18 disease, rather than treat ongoing infection, the primary analysis of the study was conducted among women who were free of infection with at least one of the relevant HPV types at the start of the trial (baseline), remained free of infection with the relevant type(s) throughout the course of the vaccination period, and who received all three doses of vaccine and placebo. Researchers analyzed the combined incidence of persistent infection, cervical intraepithelial neoplasia (CIN) or external genital lesions caused by the four vaccine HPV types (6, 11, 16 and 18) and disease caused by HPV 16 and 18.

In the primary study analysis, there were 41 cases of persistent infection, CIN or external genital lesions (genital warts and vaginal and vulvar lesions) caused by HPV 6, 11, 16 or 18 in the placebo group compared to four cases in women who received GARDASIL (91 percent reduction in incidence, 95 percent CI: 74 to 98%) over a mean of 1.65 years of follow up. Also as a primary analysis, GARDASIL prevented 83 percent (95% CI: 51 to 96%) of persistent infection, low-grade cervical abnormalities and pre-cancers, and external genital lesions caused by HPV types 16 and 18 alone (23 cases in the placebo group and four cases in the vaccine group). In a secondary endpoint, GARDASIL prevented 100 percent of persistent infections, low-grade cervical abnormalities and pre-cancers, and external genital lesions caused by HPV types 6 and 11.

In addition, GARDASIL reduced HPV 16 and 18-related abnormal Pap test results (measured as a finding of atypical squamous cells of undetermined significant, or ASC-US, with positive HPV probe, or worse diagnoses) by 94 percent (95% CI: 63 to 100%).

In this study, the most common adverse experiences were injection site-related (erythema, pain, pruritus, swelling and warmth); injection site adverse experiences were higher in the vaccine group than placebo group (76.4 percent, 64.2 percent, respectively).

GARDASIL was approved by the FDA on June 8, 2006, and is recommended for use by girls and women ages 11 to 26 by the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. GARDASIL helps protect against the four HPV types (6, 11, 16 and 18) that cause the most disease, including 70 percent of cervical cancer cases and 90 percent of cases of genital warts.

Additional important information about GARDASIL
GARDASIL is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine.

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 cancer; CIN, vulvar interepithelial neoplasia (VIN), or vaginal interepithelial neoplasia (VaIN). GARDASIL has not been shown to protect against disease due to other HPV types.

In clinical studies for GARDASIL, vaccine-related adverse experiences that were observed at a frequency of at least 1.0 percent among recipients of GARDASIL and also greater than those observed among recipients of placebo, respectively, were pain (83.9 percent vs. 75.4 percent), swelling (25.4 percent vs. 15.8 percent), erythema (24.6 percent vs. 18.4 percent), fever (10.3 percent vs. 8.6 percent), nausea (4.2 percent vs. 4.1 percent), pruritis (3.1 percent vs. 2.8 percent) and dizziness (2.8 percent vs. 2.6 percent).

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 upper arm or upper anterior thigh over a six-month period. 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 widely available throughout the United States
There is broad private and public health insurance coverage for GARDASIL. Health plans covering approximately 98 percent of privately insured lives in the U.S. (currently more than 140 insurance plans) have implemented coverage for GARDASIL; however, individual benefit coverage and rates provided by health plans may vary.

GARDASIL was also added to the Vaccines for Children (VFC) Program on November 1, 2006, providing coverage for many who do not have private health insurance.

All of the 55 immunization projects in the U.S. have adopted GARDASIL and most are filling provider orders.

Merck has a patient assistance program for vaccines. Through this program, currently available in private physicians' offices and private clinics, Merck is making available, free of charge, GARDASIL and other Merck vaccines indicated for use in individuals ages 19 and older who are uninsured and who are unable to afford vaccines.

GARDASIL is approved in 85 countries
GARDASIL (sold in some countries as SILGARD ) has been approved in 85 countries, including the United States, the 27 countries of the European Union, Mexico, Australia, Taiwan, Canada, New Zealand and Brazil, and additional applications are currently under review with regulatory agencies in many more countries around the world. Merck will donate free vaccine to the non-profit organization PATH to support demonstration studies designed to accelerate the availability of cervical cancer vaccines in the most impoverished nations. PATH is funded by a grant from the Bill & Melinda Gates Foundation. Merck is working with India's Council of Medical Research to study GARDASIL in India. At the 2007 Clinton Global Initiative, Merck committed to donate at least three million doses of GARDASIL to support vaccination programs in the lowest income nations. Merck will make its newer vaccines, including GARDASIL, available to developing world countries at dramatically lower prices at which Merck will not profit.

HPV is a common infection
In the United States, approximately 20 million people are infected with HPV, and approximately 80 percent of females will have acquired HPV by age 50. For most people, HPV goes away on its own; however in some, certain high-risk types of HPV, if unrecognized and untreated, can lead to cervical cancer. Cervical cancer is the second most common cause of cancer death in women worldwide, resulting in nearly a half-million diagnoses and 240,000 deaths each year. It is estimated that in 2007, there will be approximately 11,150 new cases of cervical cancer and 3,700 deaths in the United States. Approximately 6,000 cases of vulvar or vaginal cancer are diagnosed annually in the U.S. HPV-related diseases, including screening, follow up and treatment, costs about $5 billion per year in the U.S. HPV 16 and 18 cause an important proportion of these lesions and related costs.

Certain low-risk types of HPV cause genital warts and can lead to abnormal Pap results. Approximately one million cases of genital warts occur each year in the United States and an estimated 32 million cases occur worldwide. Additionally, there are an estimated 4.7 million abnormal Pap results that require follow-up each year in the United States. At least 3 million of these results are caused by some type of HPV.

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.