Rx Product News Profile: A Closer Look at New FDA Actions: GlaxoSmithKline's Cervarix
Cervarix (human papillomavirus bivalent [types 16 and 18] vaccine, recombinant) was approved by the FDA for use in girls and women aged 10 to 25 for the prevention of cervical precancers and cervical cancer associated with oncogenic human papillomaviras types 16 and 18.
Ms. Belisle and Dr. Patel are pharmacists at Brigham and Women’s Hospital, Boston, Massachusetts. Craig Dooley is a sixth-year PharmD candidate from Northeastern University School of Pharmacy currently on clinical clerkship in the Investigational Drug Service at Brigham and Women’s Hospital.
On October 16, 2009, the FDA approved GlaxoSmithKline’s Cervarix (human papillomavirus [HPV] bivalent [types 16 and 18] vaccine, recombinant) for use in girls and women aged 10 to 25 for the prevention of cervical precancers and cervical cancer associated with oncogenic HPV types 16 and 18.1 Cervarix is formulated with the adjuvant system AS04, composed of monophosphoryl lipid A (MPL) and aluminum hydroxide. 2
More than 100 genotypes of HPV have been identified.3 Persistent infection with HPV types 16 and 18, transmitted by sexual activity, cause about 70% of cervical cancers.3
Dosage and Administration
The dosing of Cervarix requires 3 intramuscular injections given at months 0, 1, and 6, with the preferred site of injection of the deltoid region.2
The most common adverse events were injection-site reactions, headache, and fatigue. It is recommended to observe patients for 15 minutes after injection for syncope.3
Two double-blind, randomized controlled clinical studies studied the efficacy of Cervarix to prevent cervical intraepithelial neoplasia (CIN), grades 2 and 3, or adenocarcinoma in situ. These trials enrolled a total of 19,757 women aged 15 to 25.
Study 1 was a phase 2 double-blind, multicenter, randomized, placebo-controlled trial with 1113 women who were seronegative for HPV-16 and HPV-18 at the time of vaccination.2,4 Participants were vaccinated at months 0, 1, and 6. The objective of the study was to evaluate the efficacy of the bivalent vaccine to prevent infection with HPV-16 and/or -18 between 6 and 18 months. For the study, 560 subjects were randomized to active vaccine and 553 were randomized to placebo.
To evaluate long-term safety, efficacy, and immunogenicity, a total of 776 women were also eligible for enrollment into a follow-up study (study 1 extension).3,4
Results from a combined analysis of the initial and follow-up phases indicated that the vaccine was 94.7% (3 cases in the vaccinated group vs 51 in the placebo group) and 88.5% (9 cases in the vaccinated group vs 51 in the placebo group) effective against incident infections in the per-protocol population, respectively (95% confidence interval [CI], 83.5%-98.9% and 77%-95%, respectively). 2 Cervarix efficacy against HPV- 16 and HPV-18 at 6 months in the combined analysis was 96% and 100% at 12 months (1 case in the vaccinated group vs 23 cases in the placebo group; 95% CI, 75.2%-99.9%; and 0 cases in the vaccinated group vs 9 in the placebo group; 95% CI, 52.2%-100%), respectively.3,4
Study 2 was a randomized trial that enrolled 18,644 women aged 15 to 25. The primary outcome of the study was to assess the efficacy of Cervarix against CIN grade 2+ associated with HPV type 16 or 18.2,5 The study enrolled subjects regardless of their HPV status (DNA status, HPV serostatus, or baseline cytology). 2,5 Subjects were randomized to receive Cervarix or hepatitis A vaccine (control group) at months 0, 1, and 6.2,5
Vaccine efficacy was shown to be 98.1% (96.1% CI, 88.4%-100%, P <.001) against HPV-16/18; 100% (91.0%-100%, P <.0001) against HPV-16; and 92.3% (45.7%-99.9%, P = .0009) against HPV-18. In addition, a high level of efficacy against persistent infection was noted. Vaccine efficacy was 93.8% (96.1% CI, 91.0%-95.9%, P <.0001) against 6-month persistence, and 91.2% (85.9%-94.8%, P <.0001) against 12-month persistence.5
Cervarix provides immunity against HPV types 16 and 18, known to be 2 of the more common oncogenic types.3,6 Gardasil adds immunity against types 6 and 11—2 types known to commonly cause genital warts in both men and women.3,6
The importance of the degree of immunogenicity is yet to be determined, and long-term studies evaluating duration of efficacy are necessary for both vaccines.3 â–
1. FDA approves Cervarix, GlaxoSmithKline’s cervical cancer vaccine. Available at: http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10112.htm. Accessed on February 1, 2010.
2. Cervarix [package insert]. London, UK: GlaxoSmithKline plc: 2009.
3. Hutchinson DJ, Klein KC. Human papillomavirus disease and vaccines. Am J Health-Syst Pharm. 2008;65:2105-2112.
4. Harper DM, Franco EL, Wheeler C et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection of human papillomavirus types 16 and 18 in young women: a randomized control trial. Lancet 2004;364:1757-65.
5. Paavonen J, Naud P, Salmeron J et al. Efficacy of humanpapillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomized study in young women. Lancet 2009;374:301-14.
6. Einstein MH, Baron M, Levin MJ et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years. Human Vaccines 2009;10;705-719.