FDA Expands Gardasil 9 Indication for Prevention of Select HPV-Related Head and Neck Cancers

The FDA has approved an expanded indication for Gardasil 9 for the prevention of oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) types 16, 18, 31, 33, 45, 52, and 58, according to Merck, the developer of the HPV 9-valent recombinant vaccine.¹

The indication for oropharyngeal and head and neck cancer was granted accelerated approval based on the effectiveness of the vaccine in preventing HPV-related anogenital disease. The continued approval for this indication, however, will be contingent upon the verification of clinical benefit as demonstrated in a confirmatory trial, which is currently underway.

“Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers,” Alain Luxembourg, MD, PhD, director of clinical research at Merck Research Laboratories commented in a press release.

Prior to this expanded indication, Gardasil 9 was indicated for use in girls and women between the ages of 9 and 45 to prevent cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; it was also indicated for genital warts caused by HPV types 6 and 11.² Additionally, GARDASIL 9 had indications for the following precancerous or dysplastic lesions caused by the aforementioned HPV types: cervical intraepithelial neoplasia (CIN), grade 2/3 and cervical adenocarcinoma in situ; CIN grade 1; vulvar intraepithelial neoplasia grade 2 and 3; vaginal intraepithelial neoplasia grade 2 and 3; and anal intraepithelial neoplasia (AIN) grades 1, 2, and 3.

In boys and men aged 9 through 45 years, Gardasil 9 is indicated for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58, as well as genital warts caused by HPV types 6 and 11. The vaccine is also indicated for AIN grades 1, 2, and 3 in this patient population.

The safety of the vaccine was assessed in 7 clinical trials that had collectively enrolled 15,703 individuals who had received at least 1 dose of Gardasil 9 and had safety follow-up. In Study 1 and Study 3, 7378 individuals also received at least 1 dose of Gardasil as a control and had safety follow-up.

Patients received the vaccines on the day they enrolled on the trial, with subsequent doses given approximately 2 and 6 months afterward. Investigators assessed the safety of the vaccine with the use of vaccination report card (VRC)–aided surveillance for 2 weeks after each injection of Gardasil 9 or Gardasil.

Those who underwent the VRC-aided surveillance included 9097 females aged 16 to 26 years, 1394 males aged 16 to 26 years, and 5212 males and females between the ages of 9 and 15. Of the 5212 males and females, the majority were women (n = 3436). These individuals were administered Gardasil 9 at the time of enrollment. A total of 7078 females aged 16 to 26 and 300 females aged 9 to 15 received Gardasil at enrollment.

The race distribution of the population that received Gardasil 9 proved to be comparable between females aged 16 to 26 years; 56.8% were white, 25.2% were other races or multiracial, 14.1% were Asian, and 3.9% were African American. The same held true for males and females between 9 and 15 years (62.0% white; 19.2% other races or multiracial; 13.5% Asian; and 5.4% African American) and males aged 16 through 26 years (62.1% white; 22.6% other races or multiracial; 9.8% Asian, and 5.5% African American).

In Study 1 and Study 3, the safety of Gardasil 9 was directly compared with Gardasil, and the overall race distribution of the Gardisal cohorts proved to be similar to that of the Gardasil 9 cohorts, with 57.0% of participants being white, 26.3% other races or multiracial, 13.6% Asian, and 3.2% African American.

Data pertaining to injection-site reactions, including pain, swelling, and erythema, as well as oral temperature were collected through the VRC-aided surveillance for 5 days following each injection with Gardasil 9. Among those who were given Gardasil 9, the rates of injection-site pain were comparable post-dose 1, 2, and 3. Rates of injection-site swelling and injection-site erythema, however, were found to increase following each subsequent dose.

Overall, those who received Gardasil 9 had higher rates of injection-site reactions compared with those who received Gardasil. However, few individuals discontinued the study because of adverse effects (AEs) after receiving either of the vaccines (0.1%, Gardasil 9 vs <0.1%, Gardasil).

With regard to serious AEs, of the 15,705 individuals who received Gardasil 9 and had safety follow-up, 354 experienced a serious AE, translating to 2.3% of the population. In comparison, of the 7378 individuals who were given Gardasil and had safety follow-up, 185 experienced a serious AE, translating to 2.5% of the population. Four of those who received Gardasil 9 reported at least 1 serious AE that was deemed to be associated with the vaccine. The vaccine-associated serious AEs included pyrexia, allergy to vaccine, asthmatic crisis, and headache.

Across the studies included in the safety analysis, 10 deaths were reported; 5 were reported in the Gardasil 9 group and the other 5 were reported in the Gardasil group. However, none of these deaths were determined to be related to the vaccine.

Investigators also evaluated those who were administered Gardasil 9 for new medical conditions that could potentially indicate a systemic autoimmune disorder. Results showed that 2.2% (n = 351/15,703) of those who were administered Gardasil 9 and 3.3% (n = 240/7378) of those who received Gardasil reported new medical conditions potentially indicative of systemic autoimmune disorders. These rates were similar to those previously reported.

References

1. FDA approves Merck’s GARDASIL 9 for the prevention of certain HPV-related head and neck cancers. News release. June 12, 2020. Accessed June 15, 2020. bit.ly/3hExq4q.
2. GARDASIL 9. Prescribing information. FDA; 2018. Accessed June 15, 2020. https://www.fda.gov/media/90064/download