Sanofi Pasteur MSD Release: Sustained High Efficacy of Gardasil(R) Against Early Cervical Lesions, Precancerous Vulvar and Vaginal Lesions, and Genital Warts in Longest Follow-up of Large Phase III Studies
Lisbon, 7th March 2008 – A combined analysis of three phase II/III clinical studies which enrolled more than 18,000 young women confirmed that the quadrivalent (6,11,16,18) cervical cancer vaccine Gardasil® had a sustained efficacy of 96% against early cervical lesions (CIN1 ), of 99% against genital warts and of 100% against early and precancerous vulvar and vaginal lesions (VIN 1 and 2/3, VaIN 1 and 2/3) caused by the virus types targeted by the vaccine.
These new data were presented today at the 20th European Congress of Obstetrics and Gynaecology in Lisbon, Portugal. They substantiate efficacy results against precancerous cervical lesions (CIN2/3 and AIS) already presented last month and mark the end of the clinical trials to investigate the efficacy of Gardasil® against these diseases in young women. "The new data confirm the huge benefit that quadrivalent vaccination can provide in addition to cervical cancer prevention both for women's health and for health authorities," comments lead investigator Prof. Charles Lacey, from the Hull York Medical School, University of York, UK. "Gardasil® offers a wide spectrum of protection against genital diseases caused by HPV and both an early and sustained protection which translates into rapid individual and long-lasting socio-economic benefit".
In light of the sustained high efficacy of Gardasil®, the independent Data and Safety Monitoring Board (DSMB) of the two large phase III studies in young women (FUTURE I & II) had recommended that these studies be terminated as soon as feasible in order to provide women in the placebo group with the benefits of vaccination with Gardasil®. In Europe , approximately 25% of early cervical lesions are caused by human papillomavirus (HPV) types 16 and 18 (~200,000 cases every year) and 10% more are due to HPV 6 and 11 (~80,000 cases).
Although type 6/11-related early cervical lesions usually do not progress to cancer, screening cannot distinguish them from type 16/18-related lesions which may progress to cancer. They require the same medical follow up and may lead to the same anxiety in women.
Virus types 6 /11 also cause 90% of genital warts (about 225,000 cases). , , , Genital warts can cause anxiety which may impact personal relationships. Even if effective in the short term, physically ablative therapies are painful, and recurrence rates can be high as only the visible lesion is excised while the infection persists. , , These lesions, in particular early cervical lesions and genital warts develop much faster than cervical cancer, often within a few months after exposure to the virus.
It is estimated that 30,000 new cases of pre-cancerous vulvar and vaginal lesions related to human papillomavirus are diagnosed each year in Europe. , , , An increasing incidence of pre-cancerous vulvar lesions and vulvar cancer has been noted over the past 30 years. , The incidence of vulvar carcinoma in situ increased by 400% in the United States between 1973 and 2000; invasive vulvar cancer increased by 20% during the same period. ***
About the studies
The FUTURE I and II studies (protocols 013 and 015) are phase III, prospective, double-blind, placebo-controlled randomised studies conducted in 16 countries. Over 17,000 women participated in the trials. They were aged 16 to 26 and received three doses of either Gardasil® or placebo at day 1, month 2, and month 6. FUTURE I evaluated the incidence of pre-cancerous and early cervical lesions (CIN 1-3), pre-cancerous and early vulvar and vaginal lesions (VIN1-3 and VaIN1-3) and external genital warts caused by the HPV 6, 11, 16 and 18. FUTURE II evaluated the prevention of pre-cancerous cervical lesions (CIN 2/3) and non-invasive cancers (AIS) caused by HPV types 16 and 18. The phase II clinical trial (protocol 007) was a double-blind, placebo-controlled randomised study, in which 1,106 women were enrolled. They were aged 16 to 23 years and received three doses of either Gardasil® or placebo at day 1, month 2, and month 6.
The phase II/III combined analysis is representative of 18,150 women (16–26 years) enrolled in one of the three studies and randomised to receive either Gardasil® (n = 7,864) or placebo (n = 7865) at day 1, and month 2 and 6 and were followed for up to 4 years after the start of vaccination. Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing taken at regular 6 or 12-month intervals, and collection of cervicovaginal specimens. Colposcopy referral was algorithm-based (except for protocol 007). Biopsies were HPV typed and were given histological diagnoses by a blinded gynaecologic pathology panel. Follow-up for the current analysis was 4 years post-dose 1. Analyses were carried out in a per protocol population that included subjects who received all 3 doses, had no major protocol violations, were sero and PCR-negative at day 1 and DNA negative day 1 to month 7 to the HPV vaccine types.
Notes to editors Since its first approval in 2006, Gardasil® has been approved in 93 countries and launched in 76 of them and has met with rapid adoption (more than 20 million doses distributed worldwide).
Current EU indication of Gardasil® Gardasil®, human papillomavirus vaccine [types 6,11,16,18] (recombinant, adsorbed), can be given to children and adolescents 9 to15 years and adult females 16 to 26 years of age and is indicated for the prevention of cervical carcinoma (cervical cancer), high grade cervical dysplasia CIN2/3 (precancerous cervical lesions), high grade vulvar dysplastic lesions VIN 2/3 (precancerous vulvar lesions) and external genital warts (condyloma acuminata) caused by human papillomavirus types 6, 11, 16 and 18.
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.
Contact Dr. Arne Näveke Executive Director, Communication Europe Sanofi Pasteur MSD Tel +33 4 37 28 40 40 Fax +33 4 37 28 44 04