'Merck Statement on a Potential Reduced Dosing Recommendation for GARDASIL®9'

 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today affirmed its position regarding alternate dosing regimens for GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) for the prevention of certain HPV-related cancers and diseases.

HPV vaccination has an established legacy of substantial public health impact using the currently licensed regimens, including documented reductions in certain HPV-related cervical cancers at a population level.

GARDASIL 9 is indicated for use in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal 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 also indicated for use in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal 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. The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory trial is ongoing. 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].

Merck maintains that until there are sufficient data to enable the U.S. Food and Drug Administration (FDA) and European Commission to license an alternate dosing regimen for GARDASIL 9, the Centers for Disease Control and Prevention (CDC) recommendation should remain consistent with the approved product labeling. The 2- and 3-dose regimens currently described in the U.S. and European Union product labeling were evaluated in large clinical studies that met regulatory agency standards and were extensively evaluated through the regulatory approval process. The FDA approved GARDASIL in 2006 and GARDASIL 9 in 2014. The vaccines have over 18-years and 10-years of real-world experience respectively.

As is routinely done prior to starting clinical trials, Merck sought guidance from the FDA regarding its proposed single dose trial designs to ensure they would serve as an acceptable basis for a future change to the approved dosing regimens in the label. During these discussions, the FDA was clear about the high standard of evidence that would be required for the licensure of single dose regimens. Specifically, the FDA’s feedback included the need for:

• Comparable effectiveness data of a single-dose regimen to the approved three-dose regimen;
• Demonstration that single dose efficacy is not reduced for HPV disease endpoints beyond cervical persistent infection; and
• Efficacy in men, noting there are currently no data supporting the efficacy of single-dose regimens in men.

This feedback from the FDA was highlighted in a letter shared with the CDC’s Advisory Committee on Immunization Practices (ACIP). Additional details regarding FDA comments to Merck’s two clinical trials to evaluate the potential for inclusion of a single dose regimen in the label of GARDASIL 9 can be found here.

GARDASIL, Merck’s four-valent HPV Vaccine, is not marketed in the United States.

https://www.merck.com/news/merck-statement-on-a-potential-reduced-dosing-recommendation-for-gardasil9/