FDA approves Merck’s HPV vaccine GARDASIL9

GARDASIL 9 is also approved for use in boys 9 to 15 years of age for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52 and 58, precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and genital warts caused by HPV types 6 and 11.

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

"With GARDASIL 9, the medical and public health community now has the potential to help prevent 90 percent of cervical cancers caused by HPV," said Dr. Julie Gerberding, president, Merck Vaccines.

"This is an extraordinary opportunity to even further reduce the burden of HPV-related diseases and cancers in males and females."

GARDASIL 9 includes the greatest number of HPV types in any available HPV vaccine. After HPV types 16 and 18, the five additional HPV types in GARDASIL 9 are the most common cervical cancer-causing types worldwide.

Seven HPV types in GARDASIL 9 (HPV 16, 18, 31, 33, 45, 52 and 58) cause approximately 90 percent of cervical cancer cases and approximately 80 percent of high-grade cervical lesions (cervical precancers, defined as CIN 2, CIN 3 and AIS) worldwide.

These seven HPV types also cause 85-90 percent of HPV-related vulvar cancers, 80-85 percent of HPV-related vaginal cancers, and 90-95 percent of HPV-related anal cancers. HPV types 6 and 11 cause approximately 90 percent of genital warts cases. In addition, approximately 50 percent of cases of low-grade cervical lesions (CIN 1) are caused by the nine HPV types included in the vaccine.

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) protects only against those vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52 and 58.

The U.S. Centers for Disease Control and Prevention (CDC) has made increasing HPV vaccination rates a public health priority. According to the CDC, HPV vaccination rates are unacceptably low compared to rates for other adolescent vaccines, and the CDC estimated that an additional 53,000 cases of cervical cancer could be prevented in girls 12 years and older over their lifetimes by increasing three-dose HPV vaccination coverage to 80 percent.

The CDC has also noted that for every year that HPV vaccination rates do not improve, another 4,400 women will go on to develop cervical cancer.

The CDC and other leading public health organizations, such as American Academy of Pediatrics (AAP) and National Foundation for Infectious Diseases (NFID), encourage health care providers to recommend HPV vaccine with the same sense of importance used to recommend other adolescent vaccines in order to increase vaccination rates and help protect more individuals against HPV-related cancers and other diseases.

Healthy People 2020 vaccination goals of 80 percent coverage for adolescents (13 to 15 years old) are near or have been met for all routinely recommended vaccines except for HPV vaccine. Merck anticipates that the CDC’s Advisory Committee on Immunization Practices (ACIP) will vote on recommendations for use of GARDASIL 9 at the February 2015 meeting.

"It’s remarkable to think that we now have a vaccine designed to help prevent even more cases of cervical cancer," said Elmar Joura, M.D., associate professor of gynecology and obstetrics, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria, and study investigator for GARDASIL 9. "GARDASIL 9 will have a significant impact in the fight against cervical, vaginal, vulvar and anal cancers."

GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care provider.

In clinical studies, GARDASIL 9 demonstrated high efficacy against the five additional HPV types

The clinical trial program for GARDASIL 9 was designed to build upon the efficacy established in clinical trials with GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]. The initial clinical program that supported the licensure of GARDASIL 9 began in 2007 and included five trials that evaluated more than 12,000 individuals who received GARDASIL 9.

The efficacy of GARDASIL 9 in 16- through 26-year-old girls and women was assessed in an active comparator-controlled, double-blind, randomized clinical trial (Study 1) that included a total of 14,204 women (GARDASIL 9 = 7,099; GARDASIL = 7,105) who were enrolled and vaccinated without pre-screening for the presence of HPV infection.

Participants were followed up with a median duration of 40 months (range 0 to 64 months) after the last vaccination. The primary comparison between GARDASIL 9 and GARDASIL was clinical efficacy for the five additional HPV types. Effectiveness of GARDASIL 9 against persistent infection and disease related to the original four HPV types (6, 11, 16, or 18) was inferred from non-inferiority comparisons.

The primary efficacy analysis was conducted in those who received all three doses of vaccine within one year of enrollment, did not have major deviations from the study protocol, were negative (PCR negative and seronegative) to the relevant HPV type(s) prior to dose 1, and who remained PCR negative to the relevant HPV type(s) through Month 7 (per-protocol efficacy, or PPE, population).

The primary efficacy evaluation was based on a composite clinical endpoint of HPV 31-, 33-, 45-, 52-, and 58-related cervical, vulvar, and vaginal cancer, and high-grade cervical/vulvar/vaginal disease [CIN 2/3 (cervical intraepithelial neoplasia 2/3) or AIS (adenocarcinoma in situ), VIN 2/3 (vulvar intraepithelial neoplasia 2/3), and VaIN 2/3 (vaginal intraepithelial neoplasia 2/3)].

Additional secondary endpoints related to HPV 31, 33, 45, 52, and 58 were also evaluated. Efficacy for all endpoints was measured starting after the Month 7 visit. In the PPE population, GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) demonstrated: