Landmark study for GSK’s cervical cancer vaccine published in The Lancet

Largest efficacy trial of a cervical cancer vaccine showed Cervarix® protects against the five most common cancer-causing virus types

Issued:  Tuesday 7 July 2009, London, UK

The final analysis of the largest efficacy trial of a cervical cancer vaccine is published today in The Lancet. The study, involving 18,644 women, confirmed GlaxoSmithKline’s Cervarix ^®is highly effective at protecting against the two most common cervical cancer-causing human papillomavirus (HPV) types, 16 and 18.¹ The study also showed that the vaccine provides cross-protection against HPV types 31, 33 and 45, the three most common cancer-causing virus types beyond 16 and 18.¹

Thomas Breuer, Head of Global Clinical R&D and Chief Medical Officer of GSK Biologicals commented: “These excellent study results confirm the efficacy offered by Cervarix ^® against HPV 16 and 18. For the first time the results show that this vaccine was effective against cervical pre-cancers associated with the five most common cancer-causing virus types. This is really good news for primary prevention of cervical cancer as it indicates the vaccine could offer women additional protection against cervical cancer beyond what had at first been anticipated.”

The study showed that in women who complied with the trial protocol procedures (87% of the total sample), the vaccine provided 92.9 percent protection against cervical pre-cancers (cervical intraepithelial neoplasia 2+ or CIN 2+) associated with HPV 16 or 18.¹ A further analysis of the same cohort which excluded lesions not likely to be caused by HPV 16 and 18 revealed that the vaccine was 98.1 percent effective against cervical pre-cancers (CIN 2+) caused by these two types.¹

The study showed — for the first time for any cervical cancer vaccine — that Cervarix ^® provided significant cross-protection against pre-cancerous lesions not containing HPV types 16 and/or 18.¹ This additional efficacy could translate into approximately 11-16 percent extra protection against cervical cancer over and above the protection afforded by efficacy against HPV 16 and 18 alone.¹ This effect was mainly driven by protection against HPV types 31, 33 and 45.

Professor Jorma Paavonen, from the University of Helsinki, Finland– principal investigator on the study and lead author of the publication – commented: “The results show Cervarix ^® is highly effective against the most common cervical cancer-causing virus types and has the potential to substantially reduce the incidence of cervical pre-cancers, cervical cancer and the associated diagnostic and surgical procedures. The results re-affirm confidence in vaccination as a primary preventative measure against cervical cancer when used alongside screening.”

In the study, rates of serious adverse events and medically significant conditions in the group vaccinated with Cervarix ^® were similar to the control group.¹

About HPV 008 PATRICIA (PApilloma TRIal Cervical cancer In young Adults)

• The Phase lll multi-centre, double-blind, randomised study involved a total of 18,644 women, aged between 15 and 25 years, from 14 countries across Europe, Asia-Pacific and Latin and North America¹
• Study participants were randomised to receive either Cervarix ^® or a control hepatitis A vaccine and analyses were performed in the following cohorts:¹
• • According-to-protocol cohort for efficacy (ATP-E; vaccine=8093; control=8069)
  • Total vaccinated cohort (TVC; vaccine=9319, control=9325)
  • Total vaccinated cohort-naïve (TVC-naïve; vaccine=5822; control=5819)
  • ATP-E included all women who met eligibility criteria, complied with the trial protocol and received all three doses of study vaccine¹
• TVC included all women who received at least one vaccine dose. This group comprised a diverse population of women including those with evidence of current or previous HPV infection and with high grade smear test results. This was intended to represent general population of sexually active young women¹
• TVC-na?ve included all women who received at least one vaccine dose and who had no evidence of previous or current HPV infection, and was intended to represent young girls prior to the onset of sexual activity¹
• Vaccine efficacy against CIN 2+ associated with HPV 31, 33 and 45 — HPV types not in the vaccine —was 92 percent (66.0,99.2; p<0.0001), 51.9 percent (-2.9, 78.9; p="0.0332)" and="" 100 percent (-67.8, 100, p="0.0619)" respectively in="" the="" atp-e=""></0.0001),>¹ Vaccine efficacy against CIN 2+ associated with HPV 31, 33  and 45 was 68.4 percent (34.2, 86.1; p=0•0005), 49.8 percent (4.8, 74.6; p=0.0239) and 100 percent (7.0, 100; p=0.0312) respectively in the TVC cohort¹
• Vaccine efficacy against CIN 2+ lesions associated with 12 non-vaccine cancer-causing HPV types not in the vaccine was 54 percent (34.0, 68.4; p<0.0001)  in="" the="" atp-e=""></0.0001)>¹ When excluding all CIN 2+ lesions associated with non-vaccine types in which HPV 16 and 18 was also detected, vaccine efficacy was 37.4 percent (7.4, 58.2; p=0.0092) in the ATP-E cohort.¹ These two analyses suggest that the true vaccine efficacy against CIN 2+ associated with 12 non-vaccine cancer-causing HPV types lies between 37 percent and 54 percent¹
• The vaccine also substantially reduced the number of colposcopy referral and cervical excision procedures in both the TVC and TVC-naïve cohorts
• The efficacy and safety results from the interim analysis of the HPV 008 study were previously published in The Lancet.² The data reported today are from the final event driven analysis, also published in The Lancet. Further to the final analysis, additional follow-up results will be forthcoming from the end of study

About Cervarix ^®

Cervarix ^® was specifically designed with a novel adjuvant, AS04, to deliver high and sustained levels of antibodies aimed at providing long-term protection against HPV 16 and 18, the most common cervical cancer-causing HPV types.³ It has been shown to be generally well tolerated. The most common symptoms after vaccination included pain, redness and swelling at the injection site, fatigue, fever, aching, headache, itching, rash or gastrointestinal disturbances.⁴

To date, Cervarix ^® has been approved in 97 countries around the world, including the 27 member states of the European Union (EU), Australia, Brazil, South Korea, Mexico and Taiwan. Licensing applications have been submitted in more than 20 additional countries including Japan and the United States. GSK also submitted the vaccine to the World Health Organization (WHO) for prequalification in September 2007. 

About HPV and cervical cancer

Women are at risk of HPV infection throughout their sexually active lives.⁵ Approximately 100 types of HPV have been identified to date⁶ and, of these, approximately 15 virus types are known to cause cervical cancer.⁷ HPV types 16 and 18 are responsible for approximately 70 percent of cervical cancers globally, with types 45, 31 and 33 among the next most common cervical cancer-causing HPV strains.^8,9 Persistent infection with cancer-causing HPV types can lead to abnormal Pap smears, cervical pre-cancer and cervical cancer. Cervical intraepithelial neoplasia (CIN), graded as CIN 1, 2 and 3 refers to pre-cancerous cells found on the surface of the cervix. The higher the grading number, the higher the probability the abnormal cells will become cancer cells.¹⁰ CIN 1, 2 and 3 refers to mild, moderate or severe cell changes respectively. CIN 2+ is the surrogate marker for cervical cancer. Worldwide, more than 500,000 women will be newly diagnosed with cervical cancer and 280,000 women will die from it each year.¹¹

HPV types 16, 18 and 45 are particularly important because these types are associated with nearly 90 percent of adenocarcinoma cases,⁸ a very aggressive type of cervical cancer more common in younger women and more difficult to detect through screening.^12,13

GlaxoSmithKline Biologicals –GSK Biologicals, GlaxoSmithKline’s vaccines business, is one of the world’s leading vaccine companies and a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development. Headquartered in Belgium, GSK Biologicals has 13 manufacturing sites strategically positioned around the globe. In 2008 GSK Biologicals distributed 1.1 billion doses of vaccines to 176 countries in both the developed and the developing world – an average of 3 million doses a day.

Through its accomplished and dedicated workforce, GSK Biologicals applies its expertise to discover innovative vaccines that contribute to the health and well-being of people of all generations around the world.

GlaxoSmithKline – One of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com

Cervarix ^® is a registered trademark of the GlaxoSmithKline group of companies.

Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2008.

References

1.        Paavonen J et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against cervical infection and pre-cancer caused by oncogenic HPV types: final event-driven analysis in young women (the PATRICIA trial). 2009. The Lancet.

2.        Paavonen J 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.

3.        Aguilar JC. Vaccine adjuvants revisited. Vaccine 2007; 25: 3752-3762.

4.        Descamps D, Hardt K, Spiessens B et al. Safety of human papillomavirus (HPV)-16/18 AS04 adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Human Vaccine, 2009; 55: 1-9.

5.        Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections J Clin Virol 2005; 32 Suppl 1; S16-24.

6.        WHO. Expert Committee on Biological Standardization. Guidelines to assure the quality, safety and efficacy of recombinant Human Papillomavirus virus-like particle vaccines, accessed on 27/3/2009

7.        Muñoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348: 518-527.

8.        Bosch X, Burchell A, Schiffmann M et al. Epidemiology and Natural History of Human Papillomavirus Infections and Type-Specific Implications in Cervical Neoplasia. Vaccine 26S (2008) K1–K16.

9.        Cohen J. High Hopes and Dilemmas for a Cervical Cancer Vaccine. Science 2005; 308: 618-621

10.     Cancer Research UK accessed on 11 June 2009.

11.     World Health Organization. Initiative for Vaccine Research.  Accessed on February 13, 2009.

12.     Castellsagué X et al. Worldwide Human Papillomavirus Etiology of Cervical Adenocarcinoma and Its Cofactors: Implications for Screening and Prevention. Journal of the National Cancer Institute 2006; 98 (5): 303-315.

13.     Bulk S et al. Incidence and survival rate of women with cervical cancer in the Greater Amsterdam area. British Journal of Cancer 2003; 89: 834-839.