Glaxo Boasts Cervarix Protects Against Five Most Common HPV Strains

Yet another missive has been fired in the HPV vaccine wars. A new study finds that GlaxoSmithKline's Cervarix vaccine offers protection against five of the most common strains of human papillomarvirus that can lead to cervical cancer.

The results, which were published in The Lancet on July 7, indicate the Cervarix vaccine was able to protect women from the two most common HPV strains - 16 and 18 - as well as provide protection from strains 31, 33 and 45. After strains 16 and 18, which are believed to be responsible for about 70 percent of cervical cancers globally, these HPV types are most likely to lead to cervical cancer, according to the drug maker. Combined, the five strains lead to 82 percent of cervical cancer.

In a statement, Glaxo boasted the study was the first to demonstrate that an HPV vaccine protected against pre-cancerous lesions beyond those containing strains 16 or 18. Consequently, Glaxo maintains the added efficacy could translate into 11 percent to 16 percent extra protection against HPV.

By contrast, Merck's Gardasil also protects against the 16 and 18 strains, as well as HPV strains 6 and 11, although these associated with causing genital warts, as opposed to cervical cancer. "This is really good news for primary prevention of cervical cancer as it indicates the vaccine could offer women additional protection against cervical cancer beyond what had at first been anticipated," said Tom Breuer, head of global clinical R&D and chief medical officer at GlaxoSmithKline Biologicals, in a statement.

The data is only the latest bid to dominate the competitive HPV vaccine market, where Glaxo and Merck - which markets Gardasil--are working furiously to best one another with dueling data (¹ 'The Pink Sheet,' April 6, 2009). Gardasil is approved in the U.S., the EU and other parts of the world; Cervarix is approved in 97 countries, including the EU, but has run into regulatory delays in the U.S. In Dec. 2007, the FDA issued a "complete response" letter.

Approved by FDA in 2006 for females between ages 9 and 26, Gardasil was launched amid controversy over Merck's aggressive marketing push to secure government-mandated vaccination for school-age girls. More recently, pricing and nagging safety issues contributed to a slowdown in sales - last year, Gardasil sales declined 5 percent to $1.4 billion.

Glaxo, meanwhile, re-submitted a Biologics License Application in April, which it hopes will help its chances for FDA approval of Cervarix. The BLA contains newly-released final data from this latest study; the original filing contained interim data. U.S. approval remains at least a few months away.

The data showed that Cervarix reduced the incidence of pre-cancerous lesions associated with HPV strains 16 and 18 by 93 percent, while it lowered the incidence of lesions associated with HPV strains 31, 33, 45, 52 and 58 by 53 percent. Cervarix was designed with a novel adjuvant known as AS04 to deliver sustained levels of antibodies against HPV 16 and 18 strains.

Known as PATRICIA, or PApilloma TRIal against Cancer in young Adults, the Phase III double-blind and randomized study involved 18,644 women between the ages of 15 and 25 years from 14 countries across Europe, Asia, and Latin and North America. Patients received either Cervarix or a control hepatitis A vaccine. The study was designed to test the vaccine against persistent infection and pre-cancerous lesions, and the follow-up period occurred over three years.

The lead investigator of the trial, Jorma Paavonen of the department of obstetrics and gynecology at the University of Helsinki in Finland, said some trial participants included girls and women who had no prior or current HPV infection and were never sexually active. In response to questions, he said these characteristics should allay concerns of parents who are uncertain whether to vaccinate younger daughters.

The results "suggest cervical cancer is preventable," said Paavonen, who was listed in the study as having either received honoraria, paid expert testimony or travel grants from Glaxo. "It's time to move on from the pap smear, which just detects whether the virus has already caused disease and is a secondary prevention. The primary prevention can potentially eradicate the disease. It's ready for big-time use."

For its part, Merck brushed aside the findings. In a statement sent by email, a Merck spokeswoman wrote that "Gardasil offers exceptional cervical cancer protection and has shown 98 percent efficacy against cervical caner related to HPV 16 and 18 in women 16 to 26 years of age, naive to the relevant HPV type. [And] only Gardasil protects against genital warts, which can cause significant physical, emotional and financial burden.

"While cross-protection … has been observed with both vaccines, it's important to remember that demonstration of cross protection does not make a bivalent vaccine a quadrivalent vaccine. Proven efficacy against disease caused by HPV types included in each vaccine is the most important and reliable endpoint."

In an accompanying editorial in The Lancet, a pair of researchers wrote that the HPV vaccination among girls and young women may reduce the incidence of cervical cancer "in couple of decades, [but] this subgroup of the population at risk is too small to limit the spread of the virus. The only efficient way to stop the virus is to also vaccinate the other half of the sexually active population: boys and men."

"Women have shouldered responsibility for contraception since its inception. The goal to eradicate sexually transmitted carcinogenic viruses can be jointly carried by women and men, and could be accomplished within a few decades," wrote Karin Michaels of Brigham and Women's Hospital and the Harvard School of Public Health and Harald zur Hausen of the German Cancer Research Center in Heidelberg, Germany. Both declared they have no conflicts of interest.

The newest study comes just two months after Glaxo released results of a head-to-head immunogenicity comparison between Cervarix and Merck's Gardasil. The results indicated Cervarix yielded a statistically significant and higher immune response, but didn't measure which vaccine was more effective at preventing cervical cancer or pre-cancerous lesions.

At the same time, Merck released data from an extended Phase II study showing Gardasil was effective against the HPV 16 strain for an average of 8.5 years after administration, and that women who were not exposed to 14 different HPV strains had fewer abnormal pap tests and cervical procedures (² (Also see "Sticking Point: Cervarix Outshines Gardasil, But Practical Value Is Unclear" - Pink Sheet, 8 May, 2009.)).

- Ed Silverman ([email protected])