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MIMS Supported ResourcesPHARMACOLOGY
Animal studies suggest that the efficacy of L1 virus-like particle vaccines (VLPs) is mediated by the development of an humoral immune response.
Cervarix is prepared from purified VLPs of the major capsid L1 protein of HPV types 16 and 18. These HPV types are responsible for approximately 70 per cent of cervical cancers worldwide.
CLINICAL STUDIES
The safety and efficacy of Cervarix has been assessed in over 19, 700 women aged 15—25 years in two phase II and III trials. Long-term data has been collected up to 5.5 years. Additional studies have also been conducted in girls and adolescents aged 10—14 years, and in women aged 26—55 years (ongoing).
The phase II trial1 enrolled 1113 women aged 15—25 years who tested seronegative and DNA negative for HPV-16 and 18. Three vaccinations were given, scheduled at 0, 1 and 6 months. Study duration was up to 27 months, and the primary endpoint was incident infection with HPV-16 and/or HPV-18.
Cervarix demonstrated significant efficacy against incident and persistent (secondary endpoint) HPV-16/18 infection. There were 23 cases of incident infection in the control group and two cases in the Cervarix group (91.6 per cent vaccine efficacy). Results for persistent infection were 16 cases in the control group and no cases in the Cervarix group (100 per cent vaccine efficacy).
A subset of women (n=776) vaccinated in the first trial were followed up for up to 5.5 years after the first dose.2, 3 The efficacy of Cervarix against CIN2+ (surrogate marker for cervical cancer protection) was 100 per cent. The efficacy of Cervarix against incident infection was 98 per cent; six-month persistent infection 100 per cent; 12-month persistent infection 100 per cent.3
The phase III trial4 enrolled 18,644 women (15—25 years) who received Cervarix or a control vaccine (hepatitis A vaccine) at 0, 1 and 6 months. Vaccine efficacy against CIN2+ associated with HPV-16 or 18 was assessed in women seronegative and DNA-negative for HPV-16 and 18 at baseline, including women with lesions with several oncogenic HPV types.
Interim analysis was triggered when at least 23 cases of CIN2+ with HPV-16 or 18 DNA in the lesion were detected (two cases in the Cervarix group, 21 in the cohort group). Mean length of follow-up at the time of the interim analysis was 14.8 months and vaccine efficacy against CIN2+ containing HPV-16 and 18 DNA was 90.4 per cent.
However, further analysis showed that the two cases of CIN2+ with HPV-16 or 18 in the Cervarix group and one in the control group were not considered to be causally associated with HPV-16 or HPV-18 infections.
Cervarix is formulated with an innovative adjuvant AS04. Data have shown that the antigens formulated with AS04 induced a stronger immune response when compared to the same vaccine formulated with a traditional aluminium based adjuvant.5
1. Harper DM, Franco EL, Wheeler C et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004: 364; 1757-65.
2. Harper DM, France EL, Wheeler C 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 control trial. Lancet 2006: 367; 1247-55.
3. Gall SA, Teixeira J, Wheeler WM et al. AACR, April 14-18, 2007. Abstract 4900.
4. Paavonen J, Jenkins D, Bosch FX et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 2007: 369; 2161-70.
5. Giannini SL, Hanon E, Moris P et al. Vaccine 24 2006: 5937-49.
