Regulatory Decision Summary for Gardasil 9

Authorization under the Notice of Compliance with Condition (NOC/c) policy guidance was based on biologic plausibility, supported by epidemiologic and pharmacologic data, that the surrogate endpoint of prevention of HPV-related anogenital persistent infection and disease by Gardasil 9 is logically expected to predict its effectiveness in preventing HPV-related persistent oral infection and disease.

Vaccine efficacy of Gardasil 9 in men, women, boys, and girls ages 9 to 45 years against the clinical endpoints of persistent infection, precancerous lesions, and cancers in the anogenital region has been established in clinical trials previously submitted and reviewed by Health Canada. It is reasonable to consider that these clinical endpoints are surrogates which are likely to predict protection at other mucosal sites. The pathophysiology of HPV-related transformation of squamous epithelial cells is considered to be the same irrespective of the mucosal site of infection. As a post-approval commitment under the NOC/c policy, the Sponsor will be requested to submit the final clinical study report of a phase 3, placebo-controlled, double-blind, randomized study with a primary endpoint of HPV16/18/31/33/45/52/58-related oral 6-month persistent infection, with anticipated study completion to be achieved in 4Q-2025 to confirm the clinical benefit of Gardasil 9 for prevention of head and neck cancers caused by the HPV types contained in the vaccine and to convert the NOC/c authorization to an NOC authorization.

There are no changes to the vaccine dose, components or target population and no new safety concerns associated with this proposed expanded indication. Since no new clinical studies were conducted for this submission, no new safety data were submitted for review. However, previous clinical trials of Gardasil 9, reveal the vaccine is safe and generally well tolerated, with the most commonly reported adverse events being injection site reaction, allergic reaction and syncope. Moreover, post-marketing safety studies were presented and did not revealed any new safety signals from what is already presented in the product monograph. Existing pharmacovigilance plans remains adequate, however, as an added precaution, the Sponsor will be requested to provide Periodic Safety Update Reports-Confirmatory (PSUR-C) or Periodic Benefit-Risk Evaluation Reports-Confirmatory (PBRER-C) for NOC/c on a semi-annual basis until conditions associated with the market authorization are removed.

Health Canada granted this application under the NOC/c policy.