FDA Approves Cervical Cancer Vaccine

Merck & Co., Inc. announced on June 8 that the U.S. Food and Drug Administration (FDA) approved GARDASIL® (Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine), the first and only vaccine to prevent cervical cancer and vulvar and vaginal precancers caused by HPV types 16 and 18 and to prevent low-grade and pre-cancerous lesions and genital warts caused by HPV types 6, 11, 16 and 18.

In the United States, approximately 10,000 women are diagnosed with cervical cancer every year, and an average of 10 women die each day from the disease.

The FDA approved GARDASIL for the prevention of cervical cancer; cervical pre-cancers (cervical intraepithelial neoplasia [CIN] 2/3 and adenocarcinoma in situ [AIS]); vulvar pre-cancers (vulvar intraepithelial neoplasia [VIN] 2/3); and vaginal pre-cancers (vaginal intraepithelial neoplasia [VaIN] 2/3) caused by HPV types 16 and 18. GARDASIL is also approved for the prevention of genital warts and low-grade cervical lesions (CIN 1) caused by HPV types 6, 11, 16 and 18. GARDASIL is approved for 9- to 26-year-old girls and women.

GARDASIL is designed to prevent the majority of HPV-related clinical diseases, those caused by HPV 6, 11, 16 and 18. HPV types 16 and 18 account for approximately 70% of cases of cervical cancer, AIS (non-invasive cervical cancer), CIN 3, VIN 2/3 and VaIN 2/3, and account for 50% of CIN 2 lesions. HPV 6 and 11 cause approximately 90% of genital wart cases. These four types of HPV also cause approximately 35 to 50% of all low-grade cervical, vaginal and vulvar lesions (CIN I, VIN I and VaIN I). 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. All four types cause abnormal Pap test results; the lesions caused by types 6 and 11 are clinically indistinguishable from pre-cancerous lesions caused by types 16 and 18.

The efficacy of GARDASIL, which includes results from an HPV-16 prototype of GARDASIL, was evaluated in 4 placebo-controlled, double-blind, randomized Phase II and Phase III clinical studies. Together, the Phase II and III studies evaluated 20,541 women aged 16 to 26 years. Study participants were followed for up to 5 years after enrollment.

The studies' primary analyses were conducted in women who received all 3 vaccinations within 1 year of enrollment, did not have major deviations from the study protocol and were naive to the relevant HPV type(s) prior to dose 1 and through one month post-dose three (Month 7). Efficacy was studied in the individual studies and in combined analyses and measured starting after the Month 7 visit. In the combined analyses:

GARDASIL also prevented 100% of HPV 16- and 18-related vulvar and vaginal pre-cancers (VIN 2/3 or VaIN 2/3) in women not previously exposed to the relevant HPV types. There were no cases in the 8,641 women who received GARDASIL compared to 24 cases in 8,667 women who received placebo. VIN 2/3 and VaIN 2/3 are the immediate precursors to vulvar and vaginal cancers.

These studies also showed that administration of GARDASIL to women who are already infected with one or more vaccine related HPV types prior to vaccination protects them from clinical disease caused by the remaining vaccine types but may not alter the course of an infection that is already present.

In all studies, GARDASIL was generally well tolerated and few subjects (0.1%) discontinued due to adverse events. Vaccine-related adverse experiences that were observed in clinical trials at a frequency of at least 1.0% among recipients of GARDASIL and also greater than those observed among recipients of placebo, respectively, were pain (83.9% vs. 75.4%), swelling (25.4% vs. 15.8%), erythema (24.6% vs. 18.4%), fever (10.3% vs. 8.6%), and pruritis (3.1% vs. 2.8%). Most injection-site reactions were reported to be mild to moderate in intensity.