GSK's HPV Cervical Cancer Vaccine Shows Superior Immune Response To Competitor Vaccine In First Head-to-head Study

Main Category: Cervical Cancer / HPV Vaccine
Also Included In: Clinical Trials / Drug Trials
Article Date: 11 May 2009 - 2:00 PDT

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GSK's cervical cancer vaccine, Cervarix® (Human Papillomavirus Vaccine, Types 16,18, recombinant, adjuvanted, adsorbed), is superior to Gardasil® (Human Papillomavirus Vaccine, Types 6,11,16,18, recombinant, adjuvanted, adsorbed) in generating a significantly greater antibody response at seven months in women aged 18-45 against the two main cancer causing human papillomavirus (HPV) subtypes 16 & 18. These results, from the first of its kind, head-to-head study, will be presented at the 25th International Papillomavirus Conference (IPV) in Malmö, Sweden.1

The comparative study looked at two key measures of immune response, neutralising antibodies and memory B cells, believed to play an important role in how well a vaccine will protect women from HPV infection and subsequent cervical cancer over the long term. Although, it should be noted that the minimal antibody level associated with protection against the early stages of cervical cancer are still unknown.

The trial, which was designed to show non-inferiority between the two vaccines, showed antibody levels for Cervarix® were more than two times higher than those for Gardasil for HPV type 16 and more than six times higher for HPV type 18 at seven months in all women (aged 18-45). These results were statistically significant (p<0.0001).

Results showed that at seven months Cervarix® induced 2.7 times more memory B cells than Gardasil® for both HPV types 16 and 18 (p<0.0001) in women with no detectable B-cell response before vaccination. These results are very exciting as memory B cells are critical in secreting antibodies, thus maintaining the body's first line of defence against infection. Memory B cells also help the body to swiftly generate high levels of antibodies if exposed to the virus in the future.

Dr. Anne Szarewski, Clinical Consultant at the Wolfson Institute of Preventive Medicine commented: "These results are very promising. In September 2008, the Government launched the cervical cancer vaccination programme, using Cervarix® to, vaccinate girls aged 12-13 and 17-18 against HPV. This study offers evidence for the first time that the two available HPV vaccines do not generate the same level of response against HPV 16 and 18, the two most common cancer causing virus types. Vaccines need to provide long-term protection, as women remain vulnerable to infection and potential development of related lesions throughout their life."

Tolerability and safety results of the head-to-head study showed acceptable results for both vaccines. Cervarix® did induce more localised reactions (e.g. redness and swelling at the site of injection); however, these were short-lived, with a median duration of 3.3 days or less, and did not negatively affect patient compliance. The full results from this comparative study will be published in a peer reviewed journal.

Follow-up results from a second placebo controlled study, Immunogenicity and safety of HPV-16/18 AS04-adjuvanted vaccine up to 7.3years, designed to specifically evaluate the immunogenicity and safety of Cervarix® showed that the vaccine provided high (11-13 fold above natural infection levels) and sustained antibody levels for up to 7.3 years after vaccination, the longest follow-up reported to date for any licensed cervical cancer vaccine2. In the study, Cervarix® demonstrated a favourable safety/tolerability profile

About Cervarix®

• Cervarix® has been developed to protect against infection from the two oncogenic strains of HPV, types 16 and 18, which together are responsible for 70% of cervical cancers3.


• SPC attached for further information.

About cervical cancer and HPV

• In the UK, three women die4 of and eight are diagnosed with cervical cancer every day5. It is the second most common cancer in women under the age of 35 years in the UK6.


• Cervical cancer is caused by persistent infection with oncogenic (cancer-causing) types of HPV7,8. HPV is very common and up to 75 per cent of sexually active women will be infected with HPV at some point in their lives9,10.


• Although in the majority of women, oncogenic HPV infection will be cleared by the immune system, sometimes it can persist. These women are at risk of developing cervical cancer11,12.


• There is currently no way of predicting which oncogenic HPV infections will persist or lead to cervical cancer11.


• Cervical screening is an important preventative tool against cervical cancer and the UK operates a highly effective screening programme. It has been estimated that without a screening programme, up to 5,000 more UK women would die each year from cervical cancer13.


• Regular cervical screening and a healthy lifestyle should continue after vaccination.


• For further information on cervical cancer and HPV, please refer to the accompanying backgrounder.

Overview of the first comparative clinical study

Study Design

• A comparative clinical study of Cervarix® and Gardasil® was conducted to compare immune response, tolerability and safety at month seven in females aged 18-45.


• The study is a phase III, randomised, observer-blind trial among 1,106 healthy women aged 18-45 years at 40 centres across the United States.


• The primary endpoint of the comparative study was to compare immunogenicity at month seven in females aged 18-45.


• The final analysis of the study was performed using data collected through seven months (one month after the last vaccine dose). Follow-up analyses are planned for data collected through 24 months.

References

1. Einstein M et al. Comparative Evaluation of Immongenicity of two prophylactic human papillomavirus vaccines. Presented at IPV conference Medical Meeting. 8-14 May 2009
2. N De Carvalho, C Roteli-Martins, J Teixera et al. Immunogenicity and safety of HPV 16/18- adjuvanted vaccine up to 7.3y. Presented at IPV conference Medical Meeting. 8-14 May 2009
3. Munoz N, Bosch FX, Castellsague X. Against which human papillomavirus types shall we vaccinate and screen? Int J Cancer 2004; 111: 278-85
4. Adapted from Cancer Research UK. UK Cervical Cancer mortality statistics. Cancer Research UK website.
. 5. Adapted from Cancer Research UK. UK Cervical Cancer incidence statistics. Cancer Research UK website.
6. Adapted from Cancer Research UK. Cervical Cancer Section Overview. Cancer Research UK website.
7. Walboomers JMM et al. Human Papillomavirus is a necessary cause of invasive cervical cancer worldwide. Journal of Pathology 1999; 189: 12-19
8. Bosch FX et al. The causal relationship between human papillomavirus and cervical cancer. Journal of Clinical Pathology 2002; 55: 244-65
9. Koutsky L. Epidemiology of genital human papillomavirus infection. American Journal of Medicine 1997; 102(5A): 3-8
10. Bosch FX et al. Chapter 1; HPV and cervical cancer - burden and assessment of causality. Journal of the National Cancer Institute: Monographs 2003; No. 31
11. Baseman JG, et al. The epidemiology of human papillomavirus infections. Journal of Clinical Virology 2005; 32(Suppl 1): S16-24
12. Stanley M. Immune responses to human papillomavirus. Vaccine 2006; 30: 24(Suppl 1): S16-22
13. Peto J et al. The cervical cancer epidemic that screening has prevented in the UK. The Lancet 2004; 364: 249-56