Drug products: Gardasil 9
ATC code: J07BM03
There are no published trials with the primary objective to assess sex differences in terms of pharmacokinetics, pharmacodynamics, and safety of vaccine against papilloma virus. No difference in effect has been demonstrated but the low number of men included in clinical trials can affect the ability to make statistically significant analysis.
Gardasil 9 is used in women (in Sweden) and men (in some countries) from the age of nine for prevention of precancerous anogenital (anus, cervix, vulva or vagina) lesions, anogenital cancers and external genital warts caused by the vaccine human papillomavirus (HPV) types (6, 11, 16, 18, 31, 33, 45, 52 and 58) . HPV infects the squamous epithelium in men and women, causing cervical/vulvar/vaginal cancers in women, penile cancer in men as well as anogenital condyloma acuminate, oropharyngeal and anal cancers in both men and women .
The HPV infection natural history related to age is different in men compared to women. The probability of a sexually active man acquiring a new genital HPV-infection in any given 12-month period is 0.29-0.39 per 1000 person-months, which is comparable to reported estimates for women. The rate of acquisition of new HPV-infections in men is unlike women, constant with increasing age, while it declines in women. Compared to women, older median-age at diagnosis of HPV-related cancers has been observed in men. There may be differences in the immune response to natural HPV-infection between men and women. The reported proportion of HPV seropositive men is lower than in women. Antibody titers are higher in women who are HPV seropositive and appear to provide partial protection against subsequent HPV infection, while in men antibody titers are lower and do not appear to protect against subsequent HPV infection .
No pharmacokinetics studies on the active ingredients in Gardasil 9 have been performed. This is in line with Note for guidance on preclinical pharmacological and toxicological testing of vaccines (CPMP/SWP/465/95) .
No dosage adjustment is necessary according to patient’s sex .
No studies with a clinically relevant sex analysis regarding efficacy of Gardasil 9 have been found. It should be noted that most studies include more women than men, and the low number of men included can affect the ability to make statistically significant analysis.
Seven clinical studies supported the licensure of Gardasil 9 (n=23266, 1809 males aged 9-15 years; 3498 females aged 9-15 years; 1416 males aged 16-26 and 8053 females aged 16-26 years) supporting similar immunogenicity. Efficacy against composite endpoint of CIN 2/3, and adenocarcinoma in situ as surrogate markers for cervical cancer, VIN 2/3 as surrogate marker for vulvar cancer and VaIN 2/3 as surrogate marker for vaginal cancer, was demonstrated in women 16-26 years of age with a point estimate of 96.7% (95% CI: 80.9-99.8) relative to Gardasil as the control. Protection was demonstrated for HPV vaccine types 31, 33 and 52 against endpoints of disease. Immune response comparable to previous HPV types was demonstrated against the other vaccine HPV types in the same age group. Non-inferior immune response compared to women 16-26 years has been demonstrated in males and females 9-15 years [1, 4].
No studies with a clinically relevant sex analysis regarding safety of Gardasil 9 have been found.
There are no signs that hormonal contraceptives influence the effect of Gardasil 9 . Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2017-01-09
Reviewed by: Mia von Euler, Expertrådet för vaccinationer
Approved by: Karin Schenck-Gustafsson