Marie McCullough, Philadelphia Inquirer: September 10, 2009
Government advisers yesterday recommended federal approval of Cervarix, the GlaxoSmithKline cervical cancer vaccine, after reviewing studies showing it is significantly more effective than Gardasil, the rival vaccine made by Merck & Co.
But Merck’s product, which has had a three-year head start in the U.S. market, got another boost yesterday when the committee urged the U.S. Food and Drug Administration to expand its approval for prevention of genital warts to a new market: males ages 9 to 26.
Both vaccines prevent infection with two types of human papillomavirus that cause about 80 percent of cervical cancers. Only Gardasil also protects against two types of HPV that cause 90 percent of genital warts.
While the FDA is not required to follow advisers’ recommendations, it usually does.
The latest endorsements will likely sharpen a rivalry with much local resonance. London-based GlaxoSmithKline P.L.C. directed much development of its vaccine at offices in the Philadelphia region, while Gardasil is made in and marketed from West Point, Montgomery County, home to Merck’s vaccine division.
The new studies also come as enthusiasm for HPV vaccination – hailed as a public health breakthrough three years ago – seems to be cooling amid persistent concerns about safety and questions about how long the vaccine protection will last. Gardasil’s sales slid 5 percent last year to $1.4 billion.
GlaxoSmithKline had submitted Cervarix clinical trial data and sought approval more than two years ago, but the FDA asked for more information. The agency was concerned that the vaccine’s novel “adjuvant” – a chemical that heightens immune response to the vaccine – might be triggering rare autoimmune diseases such as optic neuritis or Guillian-Barre syndrome.
In March 2009, GlaxoSmithKline submitted data from the single largest trial of a cervical cancer vaccine to date, with nearly 30,000 participants receiving Cervarix, some for as long as 6.4 years. The data showed that autoimmune diseases were not more common among vaccinated women than those in a control group.
GlaxoSmithKline also addressed another FDA concern – about spontaneous abortion. Although women were given a pregnancy test and told they should not be vaccinated if they were pregnant, about 7,200 got pregnant around the time of vaccination.
More spontaneous abortions occurred in the Cervarix group than the control group – 13 percent compared with about 9 percent – but this could have been by chance.
“I think we have to remember that both groups had lower spontaneous abortion rates than” normally occur in women in general, noted committee member Kenneth Noller, an obstetrician-gynecologist at Tufts University School of Medicine in Boston.
Like Gardasil, Cervarix is too new for scientists to know whether protection against HPV will last indefinitely. But Cervarix effectiveness data were clearly superior to those of Gardasil.
Like Gardasil, Cervarix was more than 90 percent effective at preventing precancerous lesions caused by the two “high-risk” HPV strains in women who had not been exposed to the virus before immunization. But Cervarix also was 75 percent effective at protecting against three cancer-causing HPV types that are not part of the vaccine, while Gardasil is only about 50 percent effective against one nonvaccine type.
In addition, blood tests showed that the concentration of virus-fighting antibodies was two to three times higher with Cervarix than with Gardasil – and remained high for 6.4 years.
By contrast, antibody levels fell back to natural pre-vaccination concentrations after two to three years in both males and females who had the Gardasil shots.
Merck officials say ongoing studies show that the vaccine remains effective in warding off warts and precancerous lesions despite the fall-off in antibodies. “But I would not tell you we’ll never need to give a booster shot” to Gardasil vaccines, Gregg Sylvester, Merck director of medical affairs for adult and adolescent vaccines, said in an interview after the hearing.
Others, like researcher Diana Zuckerman, say Gardasil is increasingly unappealing, especially considering that women have to continue to get regular Pap smears to screen for cervical cancer. Zuckerman is president of the National Research Center for Women and Families and a fellow at the University of Pennsylvania’s Center for Bioethics.
“Our center was excited when Gardasil was first approved, but the more we learned about how limited the data were, the more concerned we became,” she told the committee. “This is a very expensive vaccine – costing more than $400 – and we need to know how long it lasts. That’s true for women, and it’s even more true for men since the benefits are more limited. The boys of America are not facing an epidemic of genital warts.”[…]
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