SPMSD release: Gardasil
Sustained high efficacy of Gardasil® against early cervical lesions, precancerous vulvar and vaginal lesions, and genital warts in longest follow-up of large phase III studies
Final results confirm wider-ranging and earlier benefits than cervical cancer prevention alone
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
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