Results of a large multinational trial of the human papillomavirus (HPV) vaccine Cervarix indicate that it protects against more cancer-causing types of the virus than does Merck’s Gardasil, said Dr. Warner Huh, principal investigator at the UAB trial site. The GlaxoSmithKline (GSK) vaccine Cervarix contains types 16 and 18, which “constitute about 70 percent of the types that cause cervical cancer worldwide,” said Huh, a gynecologic oncologist in the UAB Department of Obstetrics and Gynecology and one of the authors of a Cervarix study published in June in The Lancet. Merck’s Gardasil, the only human papillomavirus vaccine currently approved for use in the United States, has four types: 6, 11, 16 and 18. Types 6 and 11 cause genital warts but not cervical cancer, Huh said. “What’s exciting about Cervarix is that they have evidence indicating that it protects against types that are not included in the vaccine,” Huh said. “What I mean by that is that it causes protection against types 45, 31 and 52. These are types that might be closely related to 16 and 18, but they’re not in 16 and 18. Collectively together, that may actually raise protection from 70 percent (with 16 and 18 alone) to as high as 80 percent because now you’re providing what we call cross-protection against types that are not originally included in the vaccine.” Cervarix has yet to be reviewed by the Food and Drug Administration, but it has been approved for use in Australia. The Phase III double-blind, randomized control trial was the largest of its kind to evaluate a cervical cancer prevention vaccine, Huh said. The trial was conducted on every continent except Africa, he said, and more than 18,000 women ages 15 to 25 participated, including 50 to 60 at the UAB site. “What was published in The Lancet was an interim analysis of the trial,” he said. “As part of the interim analysis, they hit a certain trigger point. Once they hit that certain trigger point, they went ahead and unblinded some of the data and looked at the results and determined what the efficacy was. What they found, essentially, was that the efficacy for the vaccine, both in prevention of HPV and also for the prevention of precancerous lesions of the cervix, was about 90 to 100 percent.” Another difference between Cervarix and Gardasil is the adjuvant, which is a molecule that causes a more robust immune response to the proteins within the vaccine, Huh said. The adjuvant in Cervarix, AS04, causes a strong response that persisted up to five years or longer in previous studies. Cervarix “is really the first true cancer prevention vaccine, and what’s exciting is that it works amazingly well. And then now you have, potentially, two independent companies that have largely created two separate products that support one another in the fact that they both clearly demonstrate high degrees of efficacy and protection in women who get the vaccine, particularly against the most common types that cause cervical cancer.” Researchers are hopeful that Cervarix will be approved in the United States for women up to age 45, as it has been in Australia, Huh said. “The reason that’s a big deal is because in this country, Gardasil is only approved up to age 26,” he said. “There is a lot of academic discussion and rationale for the use of this vaccine in older women — not just girls, adolescents and young adults — because the average age of cervical cancer is between 45 and 50. At least in Australia, they have expanded the license to give this drug to a much older age range.” He went on, “GSK submitted its Biologic License Application to the FDA for this vaccine in March of this year, so it probably will get reviewed sometime early next year. We don’t know what the age range is in terms of what they’ll ultimately get approved for by the FDA, but let’s just hypothetically say that they get approved for up to 45 years of age. That will become a big deal because then the vaccine will be, hopefully, covered and available to a much larger proportion of women in the United States.” More good news: The introduction of Cervarix in the United States is expected to drive down the price of HPV vaccines. “Cervical cancer in this country, unfortunately, is a cancer that affects the impoverished,” Huh said. “We don’t want this to be a situation of the haves and have-nots. By having a competing vaccine, we’re hoping this will ultimately drop the price of the vaccine and make it more affordable both to the private health community and also to the public health community. My hope is that the fact that there are two companies will make the vaccine more affordable over a shorter period of time.” August 2007