HPV vaccine: Will U.S. see second vaccine?
Regulatory review of a second human papillomavirus (HPV) vaccine has been delayed. GlaxoSmithKline has announced plans to submit additional data from its large-scale clinical trial for its vaccine candidate, Cervarix.
The Food and Drug Administration (FDA) delayed its review of the vaccine last year, asking the company for more information on the vaccine. Glaxo, in a June 2008 statement, said it has now answered the FDA's questions, but has decided to give the agency more data from a clinical trial that should finish by the end of this year. Glaxo submitted interim data from the trial with its initial application to the FDA in March 2007.1
To date, Glaxo's cervical cancer vaccine has been approved in 69 countries, says Liad Diamond, company spokeswoman. This number includes the 27 member countries of the European Union, Mexico, Australia, Singapore, and the Philippines. Licensing applications have been submitted in more than 35 additional countries, including Japan. The company also submitted the vaccine to the World Health Organization for prequalification in September 2007. In June 2008, the United Kingdom Department of Health named the vaccine for use in its national immunization program.2
The Cervarix vaccine is targeted to prevent infection and lesions from the two most prevalent cancer-causing types of HPV: types HPV 16 and 18. It is formulated with AS04, a proprietary adjuvant system designed to sustain antibody levels over time.
Published research indicates that the vaccine demonstrated protection up to 4.5 years against persistent infection with HPV 16 and HPV 18 and protection from pre-cancerous lesions.3 Protection also was demonstrated against infection with the third and fourth most prevalent cancer-causing types of HPV: types 45 and 31.3
Shot for older women?
In other HPV vaccine news, the FDA has delayed a decision on Merck & Co.'s application to expand marketing of its HPV vaccine, Gardasil to women, ages 27 to 45. The company filed for approval of the additional indication earlier this year.
Gardasil is approved for women ages 9-26. The Centers for Disease Control and Prevention (CDC) recommends the vaccines for all girls ages 11-12, with "catch-up" doses for those ages 13-26 who missed earlier vaccination.
At press time, the company was expected to pursue this and other supplemental approvals to extend the use of Gardasil to others, said Beverly Lybrand, a company senior vice president and general manager, in the company's announcement of the FDA delay.
Company avers safety
As use of Gardasil grows, questions have arisen regarding its safety. In June, two lawsuits were filed against the vaccine manufacturer. One lawsuit was filed on behalf of an Oklahoma girl who says she developed pancreatitis after receiving the injection.4 The other involves a Nevada girl who claims she developed Guillain-Barré syndrome as a result of the shot.4
Merck says it has analyzed the adverse events reported for the vaccine. Based on the available data, company officials say they believe that no safety issue related to the vaccine has been identified.5
Vaccine safety monitoring is administered by the Vaccine Adverse Event Reporting System (VAERS), a national program of the Centers for Disease Control and Prevention and the FDA. The agency receives reports of possible side effects that occur after people receive vaccines.
13 million doses distributed
Because the FDA first licensed Gardasil in June 2006, more than 13 million doses of Gardasil vaccine have been distributed, according to information provided by VAERS.6 Between June 8, 2006, and April 30, 2008, VAERS received 7,802 reports following Gardasil vaccination. Less than 7% reported serious side effects, about half of the average for vaccines overall, the agency states.
VAERS received 15 reports of death following Gardasil vaccination in the United States. Only 10 reports contained the level of information adequate for further analysis. "After careful review of those reports, we could not establish the causal relationship between vaccination and death," the agency reports. "For the remaining five reports of death, we were unable to obtain any patient identifying information; therefore we could not confirm death outcomes."
A total of 31 reports of Guillain-Barré syndrome (GBS) following Gardasil injection have been reported to VAERS; 10 have been confirmed. Of the 10 confirmed cases, five reported vaccination with Menactra, a meningitis vaccine, and Gardasil at the same time. Of the remaining reports, seven did not meet the case definition for the medical condition, and one had symptoms of the condition prior to vaccination. Nine cases are pending additional follow-up; four are unconfirmed reports.6
- Whalen J. U.S. approval is delayed for Glaxo's Cervarix vaccine. The Wall Street Journal, June 30, 2008. Accessed at online.wsj.com.
- Jack A. GSK wins UK cervical cancer vaccine contract. Financial Times, June 19, 2008. Accessed at www.ft.com/cms.
- Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: Follow-up from a randomised control trial. Lancet 2006; 367:1,247-1,255.
- Edelman S, Golding B. Feds' warning shot. New York Post, July 6, 2008. Accessed at www.nypost.com/seven.
- Merck & Co. Merck responds to questions about adverse events reported following vaccination with Gardasil. Press release. July 8, 2008. Accessed at www.merck.com/newsroom.
- Centers for Disease Control and Prevention. Gardasil vaccine reports to VAERS. Accessed at www.cdc.gov/vaccinesafety/vaers/gardasil.htm.