The AS04 adjuvant system used to formulate the vaccine could be contributing to the maintenance of the sustained immune response.
Cervarix, GlaxoSmithKline’s candidate human papillomavirus (HPV) L1 viruslike particle vaccine with adjuvant AS04, demonstrated 100% efficacy against precancerous lesions associated with HPV-16 and -18 over a 4½-year period, according to a published study.
Diane M. Harper, MD, MPH, gynecologic oncologist at Dartmouth Medical School, and colleagues conducted an extended follow-up analysis of women who participated in the primary efficacy study of the vaccine.
Diane M. Harper
“The results of this long-term follow-up analysis are an exciting milestone for those of us who are working to prevent cervical cancer,” Harper said in a press release. “These data illustrate that this AS04-adjuvanted candidate vaccine has so far demonstrated sustained protection against HPV-16 and -18 infections and associated cervical lesions with no evidence of waning protection for these two HPV types.”
“The vaccine is safe – long-term, 4½ years safe, not just injection-site safe,” she said. “Women do not develop any other diseases because of it.”
The study appeared in The Lancet. Harper said the data would be included in the company’s Biologics License Application to the FDA.
The primary study was a double-blind, controlled trial of 1,113 women aged 15 to 25. Researchers randomized participants to receive either three doses of the candidate vaccine or placebo at months 0, 1 and 6.
“Initial studies have provided evidence that L1 viruslike particle vaccines against HPV-16 and HPV-18 (as monovalent, bivalent or quadrivalent vaccines) prevent at least 90% of incident and persistent infections and their associated precursors of cervical cancer,” according to the study.
The trial was conducted in the United States, Canada and Brazil, and researchers evaluated the efficacy, safety and immunogenicity of the vaccine for prevention of HPV-16 and/or -18 infections, as well as associated Papanicolaou smear abnormalities and cervical lesions.
The extended follow-up examined study endpoints for 776 women from the original cohort of 1,113 for a period of up to 53 months. A total of 393 had received vaccine and 383 received placebo. Researchers conducted this study between November 2003 and July 2004.
Researchers evaluated the women for HPV DNA using cervical samples every six months during the study and performed annual cervical cytology evaluations. Researchers referred women for colposcopy following protocol guidelines. They also assessed women for long-term immunogenicity and safety.
Researchers detected HPV-16 and -18 antibodies in more than 98% of women for up to 4½ years, indicating sustained vaccine response. The vaccine demonstrated 100% efficacy against histological and cytological intraepithelial neoplasia abnormalities, according to the study.
“The AS04 adjuvant system used to formulate the vaccine could be contributing to the maintenance of the sustained immune response,” the researchers said.
Between the peak responses noted at one month after the third dose of vaccine and the end of follow-up, there was a less than 1 log10 decline in geometric mean titer values. Researchers noted a 133-fold difference between the vaccine and placebo groups’ GMT.
“The high antibody titers may indicate that the vaccine may not need to be boosted,” Harper said, compared with the tetanus vaccine, which requires a booster shot every seven to 10 years. Aluminum is the adjuvant in the tetanus vaccine.
More women in the placebo group reported adverse events associated with the shot than the vaccine group.
In addition, the vaccine demonstrated protection against HPV types 45 and 31. HPV-16, -18, -45 and -31 are collectively responsible for 80% of cervical cancers globally.
“In conclusion, immunization with the HPV-16/-18 L1 viruslike particle vaccine adjuvanted with AS04 sustained high levels of antibodies that provide protection against HPV-16 and HPV-18 associated endpoints for up to [4½] years,” the researchers wrote. “These findings set the stage for the wide-scale adoption of HPV vaccination for prevention of cervical cancer.”
Harper said the researchers will continue to follow the women for at least another year or two, perhaps longer, to monitor safety, efficacy and immunogenicity.
GSK expects to file for FDA approval for the vaccine by the end of 2006. The vaccine is under evaluation in phase-3 clinical trials that involve more than 30,000 women worldwide.
“We developed this candidate vaccine for cervical cancer with the ambition to provide women with the best possible vaccination against cervical cancer,” Philippe Monteyne, MD, PhD, head of global vaccine development at GSK Biologicals.
GSK Biologicals funded and coordinated the study.
For more information:
- Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised trial. Lancet. 2006;367:252-261.