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Cervarix & Gardasil New Studies Reported at the International Papillomavirus Conference at Malmo, Sweden
 
 
  Cervarix shows higher immune response than Gardasil - GSK

08 May 2009 www.pharmatimes.com

GlaxoSmithKline has published new data on its cervical cancer vaccine Cervarix which the firm says generated a significantly higher immune response than Merck & Co's rival product Gardasil, a claim played down by the latter company.

Results of the head-to-head clinical study, involving 1,106 women aged 18-45 and sponsored by GSK, are being presented at the International Papillomavirus Conference at Malmo, Sweden. The data shows that neutralising antibody levels for Cervarix were more than two times higher than Gardasil for human papillomavirus (HPV) type 16 and over six times higher for HPV 18. The company also noted that for HPV types 16 and 18, Cervarix induced 2.7 times more memory B cells.

Both vaccines were well tolerated, but GSK noted that rates of "solicited symptoms" were higher for Cervarix, with injection site reactions being most common. However, in both groups these symptoms tended to be of short duration.

Thomas Breuer, chief medical officer of GSK Biologicals, said that the presence of neutralising antibodies at the location of the infection, the cervix, "appears to be an important part of vaccine-induced protection against HPV". He went on to say that the study "offers the first evidence that these two vaccines do not generate the same immune response against HPV types 16 and 18, the two most common cancer-causing virus types".

However, Bennett Lee, medical director for Gardasil at Sanofi Pasteur MSD, the joint venture between Merck and Sanofi-Aventis that sells the jab in Europe, was not overly-impressed. He told Reuters that "we see no clinical relevance in the results of this study...and we don't see the point of doing such a comparison". He added that "if you want to compare vaccines, you compare clinical efficacy".

GSK will be hoping that the results of the head-to-head study will help it make up some ground on Gardasil in the cervical cancer market. Last year, sales of the latter jab brought in $1.4 billion for Merck, while Cervarix turnover reached $177 million.

Cervarix is still not available in the USA as it only completed its submission to the Food and Drug Administration in March. To date, it has been approved in 95 countries around the world, including the European Union, Australia, Brazil, South Korea, Mexico and Taiwan, and applications have been submitted in more than 20 other countries.

Back to Malmo and GSK is presenting the final analysis of the Phase III study (HPV-008) showing that Cervarix provided "a high and statistically significant level" of efficacy against pre-cancerous lesions associated with HPV 16 and HPV 18. The company will also present results from a third study show that Cervarix provided high and sustained antibody levels through the 7.3 years of follow-up after vaccination. "This is the longest follow-up reported to date for any licensed HPV vaccine", GSK concluded.


New data for GlaxoSmithKline's vaccine, Cervarix®, presented at IPV Conference - GSK Press Release

Friday 8 May 2009, London, UK & Malmo, Sweden

Key results from three important studies of the cervical cancer vaccine, Cervarix®, will be available as of today at the 25th International Papillomavirus Conference (IPV) in Malmo, Sweden.

Comparative trial of Cervarix® and Gardasil® (Study 010)

Results from the first, large-scale comparative trial between licensed human papillomavirus (HPV) vaccines show that Cervarix® generated a significantly higher immune response compared to Gardasil® .1 The comparative study looked at two key measures of immune response, neutralising antibodies and memory B cells. Although the post-vaccination immune correlates of protection for cervical cancer are still unknown, neutralising antibodies and B cells are believed to play an important role in protecting women from HPV infection and subsequent cervical cancer over the long term.2-7 Across all ages studied (women 18 - 45 years), neutralising antibody levels for Cervarix ® were more than two times higher than those for Gardasil ® for HPV type 16, and more than six times higher for HPV type 18. These results were highly statistically significant (p<0.0001).1 In addition, the proportion of women with detectable levels of neutralising antibodies in cervical secretions was higher in the group that received Cervarix® .1 Compared toGardasil® , GSK's vaccine also produced nearly three (2.7) times more memory B cells for HPV types 16 and 18.1

Compliance with the full vaccination course was high and comparable for both vaccines8 which indicates that both were well tolerated. Rates of solicited symptoms were higher for Cervarix® with injection site reactions being most common.8 However, in both groups solicited symptoms tended to be of short duration. It is expected that the full results from this comparative study will be published in a peer reviewed journal.

Thomas Breuer, Head of Global Clinical R&D and Chief Medical Officer of GSK Biologicals commented: "The presence of neutralising antibodies at the location of the infection (the cervix) appears to be an important part of vaccine-induced protection against HPV. This study offers the first evidence that these two vaccines do not generate the same immune response against HPV types 16 and 18, the two most common cancer-causing virus types. We are confident that these results, along with new results from additional key studies being presented this week, demonstrate the potential of Cervarix® ."

Phase III efficacy trial (Study 008)

Results from the final analysis of the Phase III study (HPV-008) will be presented for the first time at the conference, showing that Cervarix® provided a high and statistically significant level of efficacy against pre-cancerous lesions associated with each of the HPV types included in the vaccine (HPV 16 and HPV 18).9 In addition,the data demonstrated that the vaccine also provided type-specific protection against pre-cancerous lesions associated with some additional common cancer-causing HPV types other than HPV 16 and HPV 18.10 In women without evidence of prior cancer-causing HPV infection the overall efficacy demonstrated against any lesion, regardless of HPV type, was much greater than would be expected for a vaccine targeting only HPV types 16 and 18.11

Rates of serious adverse events and medically significant conditions were similar between study and control groups.9 These data have been submitted to regulatory authorities including the US FDA and publication is expected in a peer reviewed journal.

Long term follow up study (Study 023)

Results from a third study to be presented in Malmo show that GSK`s cervical cancer vaccine provided high and sustained antibody levels against HPV 16 and HPV 18 through the 7.3 years of follow up after vaccination. This is the longest follow up reported to date for any licensed HPV vaccine.12

Jean Stˇphenne, President and General Manager of GlaxoSmithKline Biologicals said, "Preventing cervical cancer is a public health priority in both developed and developing countries. We are pleased with these findings and how they can further the understanding of the role of Cervarix ® in helping to protect women against cervical cancer."


Glaxo Study: Cervarix Immune Response Tops Gardasil's

Dow Jones
May 08, 2009: 02:15 AM ET

GlaxoSmithKline PLC's (GSK) Cervarix vaccine induced a higher immune response in women against the virus that causes cervical cancer than Merck & Co.'s (MRK) Gardasil, according to a Glaxo-funded clinical trial.

However, the study didn't measure which vaccine was more effective at preventing actual cases of cervical cancer or pre-cancerous lesions - that would require a longer and larger trial. Both vaccines are designed to prevent infection by human papillomavirus, or HPV.

Nevertheless, U.K.-based Glaxo hopes the results, to be presented at a Swedish medical conference that begins Friday, will help give Cervarix a competitive edge if it reaches the U.S. market, which Merck has had to itself since Gardasil's launch in 2006. The U.S. Food and Drug Administration is reviewing Cervarix and could decide whether to allow it to go on sale by autumn. Cervarix is already on the market in other countries including the U.K.

"The study clearly shows a higher level of immune response in women receiving Cervarix than Gardasil," Gary Dubin, vice president of global clinical development in Glaxo's vaccine unit, told Dow Jones Newswires in an interview.

Before knowing the final data, a Merck executive played down the importance of comparing the vaccines' immune responses. "It's disease efficacy that's really the most important, and we certainly have very high efficacy against some very important disease endpoints," said Rick Haupt, program lead for HPV vaccines in Merck's research arm.

In clinical studies tested against placebo, Gardasil's efficacy rates approached 100% at preventing cervical cancer or pre-cancerous lesions that were caused by the four HPV types targeted by Gardasil. (However, there are other HPV types not targeted by Gardasil that can cause disease, and Gardasil isn't approved in the U.S. to protect against these types.)

Gardasil is marketed in most major European countries by Sanofi Pasteur MSD, a joint venture of Merck, Whitehouse Station, N.J., and France's Sanofi-Aventis SA (SNY).

Glaxo launched the head-to-head trial in the U.S. in 2007 in more than 1,100 women ages 18 to 45. The vaccines were given in three shots over six months. According to Glaxo, the women who received Cervarix had higher levels of " neutralizing antibodies," which help fight off cancer-causing HPV types, than Gardasil, one month after the last dose. For one type, the levels induced by Cervarix were more than twice as high as Gardasil and for another type they were more than six times higher, according to figures provided by Glaxo.

Glaxo said both vaccines had "acceptable" safety profiles, but rates of certain symptoms such as injection-site reactions were higher among Cervarix users. Both vaccines have been linked to headache and fainting.

The vaccines are designed differently. Cervarix has a proprietary additive known as an adjuvant, which Glaxo believes enhances its effectiveness, while Gardasil uses a more conventional adjuvant. Gardasil targets four HPV types including those that cause most cases of genital warts, while Cervarix targets two types and isn't intended to provide as much protection against warts.

Merck's Gardasil sales rose quickly after its 2006 U.S. launch but last year declined 5% to $1.4 billion as the company encountered difficulty convincing women ages 19 to 26 to get the shots. Gardasil sales recorded by Sanofi Pasteur MSD, however, jumped more than 70% to about $780 million.

Merck is trying to expand Gardasil's usage by seeking FDA approval for its use in women up to age 45 (it's now approved for 9- to 26-year-olds), and in males for the prevention of genital warts and rare cancers. Glaxo isn't seeking an indication in males.

Glaxo recorded $231 million in Cervarix sales last year.

Glaxo is set to present other data supporting Cervarix, including potential evidence that it offers some protection against additional HPV types, and that its immune-response levels last for at least 7.3 years after vaccination. Merck previously had data suggesting Gardasil could protect against additional HPV types but the FDA declined to incorporate this into the prescribing label.

Separately, Merck is presenting data showing an experimental precursor to Gardasil, a vaccine targeting just one HPV type, had sustained efficacy for an average of 8.5 years after vaccination. In another study, Gardasil reduced the number of abnormal Pap tests and subsequent procedures designed to ward off cervical cancer. Pap tests screen for cervical cancer.

By Peter Loftus, Dow Jones Newswires; 215-656-8289; peter.loftus@dowjones.com


Follow-up from the "Proof of Principle" study demonstrates sustained clinical efficacy for up to 9.5 years in the longest follow-up for any HPV vaccine

Malmo, 8th May, 2009 - 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 looked at the one-type (16) HPV "Proof of Principle" (phase II) vaccine for Gardasil® 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 of follow-up.

This is the longest protection documented for any HPV vaccine. The results were presented at the 25th International Papillomavirus Conference (IPV) in Malmo, 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 the women in the placebo group in order not to leave them unprotected any longer4,5. 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 we can be very confident today 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 unsurpassed and sustained cervical cancer protection, Gardasil® can protect from cervical, vulvar and vaginal pre-cancer, and from 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.


Strong reduction of genital warts only one year after vaccination as early benefit for both vaccinated women and health authorities investing in HPV vaccination programmes

Malmo, 8th May, 2009 - Results from an observational study in Australia establish that after only one year of a comprehensive vaccination programme with the four-type (6,11,16,18) human papillomavirus (HPV) Gardasil® major benefits are already being seen. The study results will be presented on Thursday, 14th May, at the 25th International Papillomavirus Conference - IPV - in Malmo, Sweden.

The study compared the proportion of genital warts diagnoses in the total number of diagnoses of sexually transmitted diseases at the Melbourne Sexual Health Centre before and after the introduction of vaccination with Gardasil® and documents a 48 % decline in this proportion only one year after vaccination (in women younger than 28 years).1

"Our data suggest that a relatively rapid and marked reduction in the population prevalence of genital warts among vaccinated women may be achievable through an HPV vaccination program targeting women. Our data also supports some potential benefit being conferred to men. They seem to confirm the hypothesis that the vaccination of women reduces the transmission of the virus to men", says Professor Christopher Fairley at the University of Melbourne, Australia.

Australia has distributed Gardasil® since April 2007 to school girls between 12 and 18 years and since July 2007 to women less than 26 years of age outside of the school based programme. The coverage rate in the region where the study took place is between 65 % and 75 %.

"The reduction in genital warts diagnoses is already an important benefit in itself for both women and health authorities investing in HPV vaccination programmes with Gardasil®. In addition, it is a significant marker of the whole range of benefits that a vaccination programme with Gardasil® is expected to provide, including reduced cervical cancer and cervical, vulvar and vaginal pre-cancer, says Bennett Lee, Director Medical Affairs for Gardasil® at Sanofi Pasteur MSD."

Gardasil® is the only four-type (6,11,16,18) HPV vaccine. In addition to unsurpassed and sustained cervical cancer protection, Gardasil® can protect from cervical, vulvar and vaginal pre-cancer, and from genital warts caused by HPV types 6, 11, 16 and 18. These four types together cause the vast majority of HPV-related genital diseases.2,3,4

Gardasil® is now approved in 109 countries and 44 million doses have been distributed worldwide (by the end of March 2009).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.


Glaxo's cervical cancer vaccine faces US battle

By Linda A. Johnson
AP Business Writer / May 8, 2009

TRENTON, N.J.-New studies show GlaxoSmithKline PLC's vaccine Cervarix blocks the virus that causes cervical cancer, but if it wins approval for U.S. sales, it will face an uphill battle against Gardasil, which has owned the market here for three years.

Cervarix, Glaxo's vaccine against human papilloma virus or HPV, already is approved in more than 90 other countries, but has been held up by delays in the United States. Several years ago, the British drugmaker was in a neck-and-neck race with rival Merck & Co., Gardasil's maker, to be first on the U.S. market, but it lost when Gardasil got approved in June 2006.

Late in 2007, U.S. regulators said they wouldn't approve Cervarix without additional data. from a large study still in progress at the time.

Final results from that 18,000-woman study and two others are being presented this weekend at a conference in Sweden on papillomavirus. The data was submitted to the Food and Drug Administration on March 30, and FDA is expected to decide whether to approve Cervarix within several months.

If it does, analyst Erik Gordon, a professor at the University of Michigan's Ross School of Business, said doctors who have prescribed Gardasil for a few years may see no reason to switch -- unless GlaxoSmithKline convinces them its product is much more effective or has fewer side effects.

Both vaccines target the two types of HPV that cause about 70 percent of cervical cancers, types 16 and 18, and data indicate both are about 98 percent effective. But Merck also has data showing Gardasil blocks two other HPV types that cause most cases of genital warts that Cervarix does not target.

That will be a key factor for doctors, experts said.

"All else being equal, it's a no-brainer for the doctor, (who) wants to give the most efficacious treatment," Gordon said.

Despite Merck owning the U.S. market, Gardasil racked up only $262 million in global sales in the most recent quarter, versus $320 million for Cervarix, which has won more contracts from government health programs in other countries.

Partial results of the new Cervarix studies released to The Associated Press indicate it also offers good protection against 12 other HPV types.

One of the studies, which looked at looked at levels of antibodies to some HPV types after study participants were vaccinated with Cervarix or Gardasil, found higher antibody levels induced by Cervarix. But Dr. Gary Dubin, head of one of Glaxo's clinical development centers, said that doesn't prove Cervarix is more effective.

New data will be presented at the same conference on Gardasil, indicating it blocks HPV 16 for at least 9 1/2 years, according to Merck. Glaxo has followed women for up to 7 1/2 years and continues to test some to see if they develop cervical lesions or cancer.

Dr. Cynthia Rand, a researcher, pediatrician and associate professor at the University of Rochester Medical School, said Cervarix appears to be effective. But she said the higher antibody levels triggered by Cervarix, compared with Gardasil, might be meaningless. She said doctors don't know if they will have to give booster shots years from now for either vaccine.

"It won't change my practice" of giving Gardasil and likely won't do so for other doctors, said Rand, whose university has patent claims and receives some royalties related to both vaccines. "Pediatricians prefer in general to also protect against genital warts."

 
 
 
 
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