Human Papillomavirus Vaccine Gardasil® Becomes The First Vaccine To Be Reimbursed Within The Pharmaceutical Benefits Scheme In Sweden

Main Category: Cervical Cancer / HPV Vaccine
Article Date: 17 May 2007 - 1:00 PST

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Reimbursement for girls aged 13 to 17 years in Sweden.Belgium also recommends universal human papillomavirus vaccination for young girls aged between 10 and 13 years and catch-up vaccination for girls up to the age of 15 years United Kingdom, 15 May 2007.

The Pharmaceutical Benefits Board in Sweden has included the human papillomavirus vaccine Gardasil® in the national Pharmaceutical Benefits Scheme, marking the first time that the Board has granted a vaccine reimbursement status. The reimbursement applies to girls aged 13 to 17 years.1

This decision comes less than 8 months after the licensure of Gardasil® in the European Union and 7 months after the launch of Gardasil® in Sweden. Up to now, no vaccines have been included in the Pharmaceutical Benefits Scheme in Sweden.

"This historical decision by the Pharmaceutical Benefits Board for Sweden reflects the great value of Gardasil® for women's health, a value that has been recognised already through vaccination recommendations, often coupled with reimbursement, in France, Germany, Italy, Austria, Norway, Luxemburg, the US, Australia and Canada. 15,000 women die from cervical cancer each year in Europe despite screening for early detection. This vaccine can save the lives of many women," comments Didier Hoch, President of Sanofi Pasteur MSD.

The Swedish health authorities continue their evaluation of a publicly funded human papillomavirus vaccination programme.

Belgium has also decided to recommend human papillomavirus vaccination of girls to prevent cervical cancer and other human papillomavirus diseases that occur before cervical cancer and beyond the cervix.

The High Counsel of Health (Conseil Supérieur de la Santé, CSS) in Belgium recommends universal human papillomavirus vaccination for one cohort of young girls aged between 10 and 13 years. A catch up vaccination programme for the remaining cohorts of girls up to the age of 15 years could further increase the benefit for the population and can be considered after an ongoing health-economic evaluation.

Gardasil®, Human Papillomavirus Vaccine [types 6,11,16,18], is the only licensed vaccine for the prevention of cervical cancer and other human papillomavirus diseases that occur before cervical cancer and beyond the cervix.

The human papillomavirus types 6, 11, 16 and 18 directly targeted by Gardasil® cause the vast majority of genital human papillomavirus diseases. It is estimated that human papillomavirus types 6, 11, 16 and 18 together cause 75% of cervical cancer2,, 70% of pre-cancerous (CIN‡2/3)3,4 and 50% of potentially pre-cancerous cervical lesions (CIN‡1)5, a significant proportion of vulvar and vaginal cancers and their associated pre-cancerous lesions6, 7, 8, 9, and 90% of genital warts in Europe.10, 11

In clinical studies, including more than 20,000 women, Gardasil® prevented up to 100% of cervical cancer, pre-cancerous (CIN*2/3) and potentially pre-cancerous cervical lesions (CIN*1), precancerous vulval and vaginal lesions (VIN† and VaIN‡2/3), and genital warts due to human papillomavirus virus types 6, 11, 16 and 18.12,13,14,15 a), b)

Gardasil® has been approved in 70 countries (many under accelerated review timelines), including the European Union (EU), the US, Canada and Australia and has met with very broad acceptance. Additional applications are currently under review with regulatory agencies in many more countries around the world. The EU licensed Gardasil® within just 9 months compared to a usual review time of 13-15 months. After gaining the license in September 2006 Sanofi Pasteur MSD has made Gardasil® available in 18 European countries.§

Current recommendation and funding status of human papillomavirus vaccination

In Europe, Germany, France, Italy, Austria, Norway and Luxemburg have recommended human papillomavirus vaccination of girls and young women. Decisions were taken after accelerated review times compared to decisions upon recommendations and funding for vaccination programmes against other diseases in the past.

The German health authorities recommend the universal vaccination of girls aged 12 to 17 years and add that girls and women who have not received vaccination during the recommended age period can still benefit from vaccination. Vaccination should be completed before the first sexual intercourse. Measures for the early detection of cervical cancer must continue. Since December 2006, several German health insurance funds, which together cover around 65% of the population, fully reimburse human papillomavirus vaccination. The remaining health insurance funds are anticipated to follow soon.

In Italy, the health authorities have recommended universal and free vaccination of 12 year old girls. Vaccination in the first vaccination centres at regional level is anticipated to start as of April 2007.

The French health authorities recommend the universal vaccination of 14 year old girls and also recommend offering vaccination to girls and young women aged 15 to 23 years, who have not yet had sexual relations, or in the year following the start of their sexual activity at the latest. The authorities remind that vaccination does not replace screening and that women must be screened, whether they are vaccinated or not. In February 2007, the French Health Minister had announced that the reimbursement of human papillomavirus vaccination by the National Social Security system would be decided before July 2007. In March, the French President expressed the wish that human papillomavirus vaccination should be reimbursed under the best conditions and as fast as possible.

In Norway, the health authorities recommend the universal vaccination of 12 year old girls and a catch-up vaccination programme for girls up to the age of 16 years.

In Luxemburg, the health authorities recommend the universal vaccination of 12 year old girls and a catch-up vaccination programme for girls up to the age of 18 years.

In Austria vaccination is recommended for girls and boys aged 9 to 15 years as well as for women, preferably before the start of sexual activity.

In June 2006, the US health authorities recommended the routine vaccination of girls aged 11 to 12 years and the vaccination of girls and women aged 13 to 26 years who have not previously been vaccinated and that girls aged 9 to 10 years can be vaccinated at the discretion of their physicians. Pap** and human papillomavirus screening prior to vaccination are not necessary according to the recommendation. The US authorities also recommended that females can receive Gardasil® regardless of whether they have or previously had an abnormal Pap test, a positive human papillomavirus test or genital warts. In the meantime, health insurers covering approximately 98% of privately insured lives in the US have implemented coverage for Gardasil®. In November 2006, the authorities added Gardasil® to their Vaccines for Children (VFC) contract providing coverage for many who do not have private health insurance. All of the 55 immunisation projects in the US have adopted Gardasil®.

In November 2006, the Australian government announced the funding of Gardasil® for girls and women aged 12 to 26 years from 2007. Gardasil® will be put on the national immunisation programme for girls aged 12 to 13 years to be delivered through schools. The government will also fund a two year catch-up programme for girls aged 13 to 18 years in schools and women aged 18 to 26 years to be delivered through general practitioners.

As of 15th February 2007, Gardasil® is recommended in Canada for girls and women aged between 9 to 26 years. Females who had previous Pap abnormalities including cervical cancer or have had genital warts or known human papillomavirus infection would still benefit from Gardasil® according to the recommendations of the Canadian authorities.

The burden of cervical cancer and other human papillomavirus diseases

Despite screening for early detection, cervical cancer remains the second most common cause of death from cancer (after breast cancer) among young women (aged 15 to 44 years) in Europe††.16 Around 33,500 women are diagnosed with, and 15,000 women die from cervical cancer each year (the equivalent of 40 women per day or nearly 2 per hour).17

In addition, hundreds of thousands of women are diagnosed with other human papillomavirus diseases that start before cervical cancer and go beyond the cervix. These diseases include pre-cancerous and potentially pre-cancerous cervical lesions3,5,18, vulvar and vaginal cancer6, 7, 19, pre-cancerous vulvar and vaginal lesions8,9,20,21 and genital warts.22

Cervical cancer is caused by human papillomavirus.‡‡23,24 The virus is very common, with 70% of sexually active people estimated to become exposed at some point in life.25,26,27 Genital infections with human papillomavirus are very common with the majority of infections occurring in adolescence or early adulthood.28,29

EU indication of Gardasil®

According to the licence in the EU, Gardasil®, Human Papillomavirus Vaccine [types 6,11,16,18] (Recombinant, adsorbed), can be given to children and adolescents age 9 to15 years and women aged 16 to 26 years 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.

Worldwide availability of Gardasil®

Gardasil® has been developed by Merck & Co., Inc. and Sanofi Pasteur MSD. In Europe, the vaccine is marketed by Sanofi Pasteur MSD.

Merck is actively working to accelerate the availability of Gardasil® in the developing world. Clinical trials for the development of Gardasil® have already included participants from 33 countries on 5 continents in a variety of settings. Clinical studies in developing world countries are being initiated to assess the efficacy of Gardasil® in other environments. Merck will donate free vaccine to the non-profit organisation PATH§§ to support demonstration studies to accelerate the availability of human papillomavirus vaccines in the most impoverished countries. Merck is also working with India's Council of Medical Research to study Gardasil® in India. Merck will make our new vaccines, including Gardasil®, available to developing world countries at dramatically lower prices.

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. www.apmsd.co.uk

Clinical study details

a) FUTURE I and II are phase III, prospective, double-blind, placebo-controlled randomised studies conducted in 16 countries. The women who participated in the trials were aged 16 to 26 and received three doses of either Gardasil® or placebo at day 1, month 2, and month 6. The primary analyses of these trials evaluated the efficacy of Gardasil® compared to placebo in women who were negative to the relevant human papillomavirus types (6, 11, 16 and/or 18) when they started the study, remained free of infection with the relevant human papillomavirus types through month 7, received all three doses of Gardasil® within one year and had no protocol violations.

FUTURE I evaluated the incidence of pre-cancerous and potentially pre-cancerous cervical lesions (CIN 1-3), pre-cancerous and potentially pre-cancerous vulvar and vaginal lesions (VIN1-3 and VaIN1-3) and external genital warts caused by the human papillomavirus types 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 human papillomavirus types 16 and 18.

b) 20,541 women (16-26 years) from the Americas, Europe and Asia were enrolled in one of four trials. In one trial, subjects were randomised to either a monovalent human papillomavirus 16 vaccine or placebo. In 3 trials, subjects were randomised to either Gardasil® (types 6/11/16/18) or placebo. For all trials, vaccination occurred at day 1, and months 2 and 6. The primary endpoint was the combined incidence of human papillomavirus types 16/18-related CIN 2/3, AIS, or cervical cancer. In the human papillomavirus 16 vaccine study, only human papillomavirus 16-related cases were considered. Analyses were done in a per protocol (PP) population (subjects received 3 doses, had no major protocol violations, were human papillomavirus 16/18 seronegative at day 1 and human papillomavirus 16/18 DNA negative Day 1 through month 7). Endpoint counts began at Month 7.

* Cervical Intraepithelial Neoplasia
† Vulvar Intraepithelial Neoplasia
‡ Vaginal Intraepithelial Neoplasia
§ Austria, Belgium, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Liechtenstein, Luxemburg, Netherlands, Norway, Portugal, Sweden, Switzerland, United Kingdom.
** Cytological screening, named after its inventor George Papanicolaou.
†† European Union 25 member states plus Iceland, Norway & Switzerland
‡‡ 99.7% of cervical cancers contain the genetic material (DNA) of the virus
§§ Program for Appropriate Technology in Health

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