New Study Results Further Support The Evidence That The HPV Vaccine Gardasil(R)will Provide Long-lasting Protection

Main Category: Cervical Cancer / HPV Vaccine
Article Date: 11 May 2009 - 5:00 PDT

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New results from an extended follow-up study further support the evidence that protection provided by the four-type (6,11,16,18) human papillomavirus (HPV) vaccine Gardasil® should be long-lasting.

The study, which was part of the clinical development programme for the quadrivalent vaccine, looked at the one-type (16) HPV "Proof of Principle" (phase II) vaccine and found that on average 8 years and up to 9.5 years after vaccination there was no HPV-16-related clinical disease (cervical lesions or pre-cancer*) in the vaccine group.1 All observed disease occurred in the placebo group. For some women, follow up has already reached 9.5 years.

This is the longest protection documented for any HPV vaccine. The results will be presented at the 25th International Papillomavirus Conference (IPV) in Malmö, Sweden.

Gardasil® has demonstrated sustained protection in phase II and phase III clinical studies for up to five and four years respectively2,3 before independent experts recommended ending the follow-up and vaccinating women in the placebo group, believing it unethical to deny them the benefit of an effective vaccine4,5. In addition, the vaccine has demonstrated immune memory which experts consider a hallmark of long-term protection.6

"Health authorities around the world have implemented HPV vaccination with Gardasil® based on robust evidence for high and sustained protection. The new results bring a new piece of evidence. In addition, the follow-up of a large cohort of women vaccinated with Gardasil® in the phase III clinical programme continues. These data suggest that today we can be very confident in the sustainability of the protection provided by Gardasil®", says Professor Margaret Stanley, from the University of Cambridge in the United Kingdom.

Gardasil® is the only four-type (6,11,16,18) HPV vaccine. In addition to sustained cervical cancer protection, Gardasil® can protect against cervical, vulval and vaginal pre-cancers, and against genital warts caused by HPV types 6, 11, 16 and 18. These four types together cause the vast majority of HPV-related genital diseases.7,8,9

Gardasil® is now approved in 109 countries and 44 million doses have been distributed worldwide since launch in June 2006 and until the end of March 2009.

Notes

HPV vaccination is now recommended in 18 of the 19 European countries in which Sanofi Pasteur MSD markets Gardasil®, and is funded or due to be funded soon in 16 of them†. HPV vaccination is also recommended and funded in the US, Australia, New Zealand and Canada. In the UK, a national immunisation programme using a bivalent HPV vaccine is in operation.

Details about the new follow-up study

Between March 2006 and May 2008, 290 women who had participated in a phase IIb Randomised Control Trials of a prophylactic HPV 16 L1 VLP vaccine in Seattle were enrolled in an extended follow-up study. While the average follow-up time was 8 years after for vaccination for 19 women follow-up has already reached 9.5 years. The results showed that no women developed either HPV 16 infection or HPV 16 associated CIN in the vaccine group. In the placebo group 6 women developed HPV 16 infection and 3 women developed HPV 16 associated CIN1 . None of the vaccine recipients who were negative for anti HPV 16 antibodies during the extended follow up period became infected with HPV 1610.

Gardasil® has demonstrated a good safety profile

Almost three years after the first launch and with 44 million doses distributed worldwide (by the end of March 2009) health care professional have extensive experience with the administration of Gardasil®. Authorities around the world‡ have confirmed the good safety profile of Gardasil®11,12 ,13,14 ,15,16. In January 2009, the Global Advisory Committee for Vaccine Safety (GACVS) of the World Health Organisation (WHO) stated that "the safety profile is similar to that described in the clinical trials before its licensing. There is no evidence of new side effects not previously detected, in relation with the use of this vaccine".17

Large clinical studies that lasted a decade and included more than 25,000 women in 33 countries have not revealed an increased risk of serious adverse events compared to placebo18,19,20. In clinical trials the most often reported adverse events were injection site reactions and fever.

Indication of Gardasil®

Gardasil® is a vaccine for the prevention of premalignant genital lesions (cervical, vulvar and vaginal), cervical cancer and external genital warts (condyloma acuminata) causally related to Human Papillomavirus (HPV) types 6, 11, 16 and 18. The indication is based on the demonstration of efficacy of Gardasil® in adult females 16 to 26 years of age and on the demonstration of immunogenicity of Gardasil® in 9- to 15-year old children and adolescents. Protective efficacy has not been evaluated in males. The use of Gardasil® should be in accordance with official recommendations.

About Sanofi Pasteur MSD

Sanofi Pasteur MSD is a joint venture between sanofi pasteur, the vaccine division of sanofi-aventis, and Merck & Co., Inc. Combining innovation and expertise, Sanofi Pasteur MSD is the only company in Europe dedicated exclusively to vaccines. Sanofi Pasteur MSD is able to draw on the research expertise of sanofi pasteur and Merck & Co., Inc., together with their teams throughout the world, to focus on the development of new vaccines for Europe, which aim to extend protection to other diseases and perfect existing vaccines in order to improve the acceptability, efficacy and tolerability of vaccination.

† Austria, Belgium, Denmark, France, Germany, Greece, Iceland, Ireland, Italy, Liechtenstein, Luxemburg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom; only Finland has not yet recommended HPV vaccination; only Austria, Ireland and Finland have not yet decided on funding.
‡ including the U.S. CDC and Food and Drug Administration (FDA), the European Medicines Agency (EMEA), the Australian Therapeutic Goods Administration (TGA), the French Agency for Sanitary Security of Health Products (AFSSAPS), the German Government and the Swiss regulatory agency (Swissmedic)

References

1. Rowhani-Rahbar, A et al. Long-term efficacy of a prophylactic human papillomavirus type 16 vaccine. 25th International Papillomavirus Conference, May 8-14 Malmö, Sweden

2. LL Villa et al. Five years efficacy of a quadrivalent HPV vaccine, Br J Cancer 2006; 95(11):1459-1466

3. Lacey JN for the GARDASIL Phase II/III Investigators. Continued efficacy of quadrivalent hpv (types 6/11/16/18)L1 VLP vaccine in preventing cervical or external genital disease: 4 years of follow-up, poster with discussion, EBCOG, Lisbon, March 4-8, 2008

4. Sanofi Pasteur MSD, data on file

5. Joura EA et al. Sustained protection by quadrivalent HPV (type 6, 11, 16, 18) vaccine through 4 years against HPV 6/11/16/18- related cervical intraepithelial neoplasia grade 2/3 (CIN2/3) and adenocarcinoma in situ (AIS) of the cervix; Abstract presented at the 19th International Congress on Anti-Cancer Treatment (ICACT), 5-8 February 2008, Paris, France.

6. Olsson SE et al. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine 2007; 25:4931-4939

7. Smith JS et al. Human papillomavirus type distribution in invasive cervical cancer and highgrade cervical lesions: A meta-analysis update. Int J Cancer 2007; 121:621-632

8. Gardasil®, Summary of Product Characteristics 2009,

9. Gardasil®, European Product Assessment Report (EPAR), Scientific Discussion, http://www.emea.europa.eu/humandocs/PDFs/EPAR/gardasil/070306en6.pdf (Last accessed May 5th 2009)

10. Sanofi Pasteur MSD Data on file - 2009

11. http://www.cdc.gov/vaccinesafety/vaers/FDA_and_CDC_Statement.htm (Last accessed May 5th 2009)

12. http://www.emea.europa.eu/humandocs/PDFs/EPAR/gardasil/Gardasil_press_release.pdf(Last accessed May 5th 2009).

13. http://www.tga.gov.au/alerts/medicines/gardasil.htm (Last accessed May 5th 2009)

14. http://www.afssaps.fr/Infos-de-securite/Communiques-de-presse/Gardasil-R-premier-bilan-de-la-surveillance-des-risques-en-France/(language)/fre-FR(Last accessed May 5th 2009)

15. http://www.bundestag.de/aktuell/hib/2008/2008_173/11.html (Last accessed May 5th 2009)

16. http://www.swissmedic.ch/aktuell/00003/00559/index.html?lang=de (Last accessed May 5th 2009)

17. WHO Weekly epidemiological record, No 5,2009,84,37-40 http://www.who.int/wer/2009/wer8405.pdf (Last accessed May 5th 2009)

18. The Future II Study Group. N Engl J Med 2007; 356: 1928-43

19. Garland et al, The Future I Investigators. N Engl J Med 2007; 356: 1928-43

20. Barr E, Tamms G. Quadrivalent Human Papillomavirus Vaccine. Clinical Infectious Diseases 2007; 45:609-17

Source
Sanofi Pasteur MSD