Cervical cancer may cease to be the killer it was once renowned to be. Two new vaccines are attempting to change the natural course of this deadly cancer, Gardasil from Merck & Co and sanofi-aventis, and Cervarix from GlaxoSmithKline.
Gardasil was launched in its first market, the USA, in June 2006 and by the end of July 2007, had been approved in a total of 80 countries and launched in almost 60. Cervarix, while lagging somewhat behind, was approved in its first market, Australia, in May 2007 and in September 2007 was approved in the EU; GSK finally filed a BLA with the FDA for Cervarix in March 2007.
Wayne Pisano, President & CEO of sanofi pasteur, the vaccines unit of sanofi-aventis, speaking in an interview with IMS in April 2007, noted: "Gardasil is highly significant for women's health globally and obviously in Europe. Therefore, Gardasil is expected to contribute significantly to the growth of Sanofi Pasteur MSD, Merck and sanofi-pasteur. Financial analysts see a several billion Euro market for human papillomavirus vaccines, with a considerable contribution from Europe and a lion's share for Gardasil thanks to its unique profile. The main issue with Gardasil is getting appropriate reimbursement, but what we've seen so far in Europe has been encouraging."
Sales of Gardasil in Europe were €81 million in the first six months of 2007 - slightly ahead of expectations. It is marketed there by Sanofi Pasteur MSD, the joint venture with Merck & Co.
Launch data - Gardasil versus Cervarix
|
Vaccine |
US status |
EU status |
Asia status |
Indication |
|
Gardasil |
Launched |
Launched |
Launched |
Prevention of: cervical cancer; pre-cancerous cervical lesions CIN2/3; precancerous vulvar lesions (VIN2/3); genital warts caused by HPV types 6,11,16,18 |
|
Cervarix |
Filed |
Approved |
Launched Australia, Philippines, filed in Japan |
Prevention of: CIN2/3; cervical cancer causally related to HPV types 16, 18 |
Source: IMS R&D Focus
Morgan Stanley believe that peak sales of Gardasil could exceed $2 billion and are of the opinion that it could be the largest selling vaccine ever; Merrill Lynch are even more optimistic, seeing sales surpassing the $4.5 billion mark. Cervarix, meanwhile, is seen by many analysts as GSK's biggest near-term pipeline opportunity, with sales possibly surpassing $2.5 billion.
According to Morgan Stanley, HPV causes approximately 10% of all cancers globally and the new vaccines have the potential to reduce this incidence markedly. Morgan Stanley say that on one hand, Cervarix can be positioned more purely as a vaccine for the prevention of cancer. The protection against genital warts offered by Gardasil, however, offers a direct advantage for males to be vaccinated (genital wart prevention is the most compelling reason for use in men) and represents a broader potential market.
How do Gardasil and Cervarix differ?
Both Gardasil and Cervarix are effective against HPV types 16 and 18, but in addition, Gardasil is effective against HPV types 6 and 11, which cause genital warts (and early cervical lesions). Gardasil has been approved for females aged 9-26 and boys aged 9-15 (the latter in Europe), while Cervarix has been licensed for females aged 10-45.
Cervarix uses a novel adjuvant (AS04), which gives a faster, stronger and longer immune response than conventional aluminium-based adjuvants. GSK hopes to distinguish Cervarix from Gardasil in several ways, including promoting it as having broader protection against the virus strains that cause cervical cancer, and getting approval to market Cervarix to women through middle age.
MedImmune, now owned by AstraZeneca, co-developed Cervarix. In 2005 GSK signed a cross-licensing and settlement agreement with Merck & Co regarding certain patent rights related to their respective HPV vaccines. Under this agreement, GSK will receive an upfront payment and royalties from Merck & Co based upon sales of Gardasil. Further financial details were not disclosed.
According to a report published by the American Academy of Microbiology (AAM) in 2005, the duration of immunity offered by the HPV vaccines is not known, but it is thought that the antibodies for HPV last for a number of years. Both Gardasil and Cervarix have been shown to be very effective and safe - both have shown 100% efficacy in preventing changes in the cervical cells that signal the development of cancer.
What problems could manufacturers face?
The use of cervical cancer vaccines, however, could be controversial. Although teenagers and adults took part in the trials, in practice the vaccine is likely to be administered to girls as young as 9-13. Some critics have argued that treating young girls with the vaccine might encourage under-age sex.
According to a report published by the AAM in 2005, "economic barriers include the current pricing structure, a system that often fails to adequately compensate the companies that develop vaccines in the early years following licensure. Governments and other purchasers must realize that the development and production of vaccines could be severely hampered if better recovery of costs is not realized."
Sanofi Pasteur MSD, using data from France, hypothesised that vaccination against HPV types 6, 11, 16 and 18 could save the French government about €70 million per year in healthcare costs in the mid-long term, and as much as €18 million as of the sixth year following vaccination and €29 million in the tenth year, thus providing a very early clinical and economic benefit. Moreover, some 90% of the cost avoided in the first years are related to the prevention of HPV types 6 and 11, showing that the prevention of early cervical lesions (CIN1) and genital warts is providing an early benefit of vaccine implementation. (This simulation is underestimated, as it does not take into account all HPV-related direct costs, such as ambulatory costs for cervical cancer, vulvar and vaginal cancers or lesions, or indirect costs such as productivity loss.)
Will governments reimburse?
In Europe, Gardasil has been priced at €300-360, a slight premium to the US price of $360 (for the three-dose treatment). The cost of Cervarix in Australia is A$460 ($335) for the full course.
Many countries, including the USA, Canada, Australia and several EU member states, already recommend routine HPV vaccination for pre-adolescent girls, usually coupled with catch-up programmes for adolescent girls and young women. Several of these countries, including the USA, Australia, Germany, France, Sweden and Italy, also already reimburse vaccination, or have started publicly-funded vaccination programmes.
HPV 16/18 responsible for up to 75% of cases
Within Europe alone, cervical cancer is the second most common cause of death from cancer among young women, with 33,500 women diagnosed each year. Of these, some 15,000 die, or nearly 40 per day. Within the USA, some 14,000 women are diagnosed with cervical cancer each year, some 3,900 of whom die from the disease.
HPV has been identified as the cause of the majority of cervical cancers. Vaccination against the two most common HPV types (16 and 18) may eradicate up to 75% of cervical cancers, as well as prevent HPV-related pre-cancers, and other cancers, including vagina and vulvar cancers and oropharyngeal cancer; HPV 16 accounts for 50-60% of all cervical cancers worldwide and HPV 18 for a further 15-20%).
According to the results of a study published in the Journal of the American Medical Association, the combined prevalence of HPV types 16 and 18 is about 2% of the female population aged 14-59. The US Centres for Disease Control & Prevention said in February 2007 that the prevalence of HPV was highest among those aged 20-25, with 44.8% infected and nearly a quarter of teenagers aged 14-19 infected. Using data from a group of 1,921 girls and women aged 14-49, researchers found that 26.8% were infected with any type of the virus. This rate translates to a total of 24.9 million girls and women in the USA alone. The infection rate hovered at about 1 in 4 for older age groups until the 50-59 age group, where 1 in 5 was infected.
Men are also susceptible to the disease and may develop genital warts as a result. A link has been suggested between the presence of HPV and oropharyngeal cancer. According to data presented at the American Society of Cancer meeting in June 2007, HPV 16 has been shown to be associated with approximately 90% of HPV-induced oropharyngeal cancers. Having serotype HPV 16 in these vaccines could therefore offer the potential for cross-over protection against oropharyngeal cancer when vaccinating. This may be the ammunition that the manufacturers need to push for approval in men, thereby increasing their market size.
Other companies are now following Merck & Co, sanofi-aventis and GSK into the area of cervical vaccines. Transgene, for example, is running Phase II trials with TG 4001, which was licensed to Roche (as R3484) in April 2007. Jean-Yves Bonnefoy, R&D Director at Transgene, presenting at the World Vaccine Conference in Lyon in October 2006, said TG 4001 is proving to be safe and effective. The vaccine differs from Cervarix and Gardasil in that it has been shown to be effective in treating established infections, whereas neither Cervarix nor Gardasil have shown efficacy in this respect.
It will be many years before the current screening programmes for cervical cancer - a cause of anxiety to many women - can be scaled down. But the new vaccines against HPV offer hope that this major killer of women is finally beginning to be controlled, and most importantly, prevented.
Part II: Cervical cancer vaccines in the developing world
This article was written by Dr Nora McCarthy, Executive Editor of IMS Company Profiles. Covering more than 80 of the top pharmaceutical and biotechnology companies, the profiles offer authoritative insight into company strategy, finances, portfolio management, R&D and history and also contain top-line IMS sales data. For more information, please contact Stephanie Earle or call +44 203 075 5757.