It's being called a cancer vaccine for women — and a landmark to boot. But it could equally be seen as a vaccine against sexually transmitted disease and the likelihood is that it will be just as effective in men.
That's because Gardasil works by boosting the immune system so that it effectively fights off four types of human papillomavirus, the most prevalent STD in modern society. In North America, HPV is said to infect half of all sexually active women between 18 and 22.
In most women, HPV clears up on its own but for some, the infection persists and can lead a couple of decades later, when they are in their prime child-rearing years, directly to cervical cancer, one of the top killers of women around the world.
By most estimates as many as 250,000 women, most of them in less-developed countries, die each year of cervical cancer and French researchers have said that number could jump fourfold by 2050 if nothing is done.
In Canada, about 400 die from the disease each year and another 1,350 or so are diagnosed with it. Health Canada has followed the U.S. decision. It recommends Gardasil for use on girls and women aged nine to 26. The vaccine is most effective before sexual activity begins.
Health Canada gave the approval on July 18, 2006, and the vaccine is now available through Canadian doctors and pharmacists. By 2008, all provinces had school-based vaccination programs for Gardasil.
World's most costly vaccine
However, the decision is not without controversy. At $360 US for a course of three treatments, Gardasil takes its place as the most costly vaccine on the planet.
For manufacturer Merck & Co., the giant drug-maker that is still reeling from the recall of its once celebrated painkiller Vioxx, Gardasil is seen as something of a corporate life raft.
Gardasil had 2007 sales of $1.5 billion US, but sales began slowing in the second half of 2008, after a U.S. government-funded Harvard study concluded it was cost-effective for girls but not for women in their 20s.
Merck could find its revenues significantly boosted if it is allowed to administer the vaccine to young men. (The issue with men seems to be simply one of sufficient testing: until fairly recently, researchers report, men have rebelled against having swabs taken from the inside of their penises.)
The vaccine manufacturer asked the FDA in December 2008 to allow it to dispense Gardasil to males. The FDA has scheduled a Sept. 9, 2009 date for an advisory panel to review the use of Gardasil, including whether it should be given to males.
Merck had also requested that the use of the vaccine be expanded to include women aged 27-45, but in January 2009, the FDA denied that request, asking Merck to provide longer-term data on women in that age range. Merck expects to give a response in the fourth quarter of 2009.
The value of the drug could go up if a growing lobby of health groups has its way. Already U.S. doctors are saying that leaving Gardasil to those families with private insurance or hit-and-miss government programs is creating an unconscionable Sophie's choice or roulette game in which certain young women would be left vulnerable to a preventable type of cancer and others are not.
Marketing ruffles feathers
Merck has also drawn fire for its efforts to promote the vaccine.
An editorial published on Aug. 19, 2009, in the Journal of American Medical Association questioned Merck's marketing strategy when it comes to Gardasil, particularly its funding of major U.S. medical groups.
"The vaccine manufacturer also provided educational grants to professional medical associations (PMAs) concerned with adolescent and women's health and oncology," wrote Sheila Rothman and David J. Rothman.
They say Merck funded the American College Health Association, the American Society for Colposcopy and Cervical Pathology, and the Society of Gynecologic Oncologists.
"The funding encouraged many PMAs to create educational programs and product-specific speakers' bureaus to promote vaccine use. However, much of the material did not address the full complexity of the issues surrounding the vaccine and did not provide balanced recommendations on risks and benefits."
Merck told the Washington Post in an interview it had given $199,000 US to the American College Health Association, $300,000 to the American Society for Colposcopy and Cervical Pathology and $250,000 to the Society of Gynecologic Oncologists.
The company maintains it did not direct the groups on how that money should be spent.
National vaccination program
In Canada, the federal government announced in its March 2007 budget that $300 million over three years will be available to the provinces and territories in support of a national vaccination program. The Conservative government noted that when new vaccines become available, it's critical to make them available to Canadians as soon as possible.
On June 20, 2007, the Nova Scotia government announced Gardasil will be offered to seventh grade girls as part of the school-based vaccination program and will not be mandatory. In 2008, about 50 per cent of eligible girls were vaccinated in Ontario, though uptake was 80 per cent in Nova Scotia, according to an editorial in the Sept. 1 online issue of the Canadian Medical Association Journal.
The catch with Gardasil, though, is that it has proved remarkably effective against two particular strains of HPV, which in themselves are said to be responsible for upwards of 70 per cent of cervical cancers. That means Gardasil will not prevent all cervical cancers and women are still advised to get Pap tests.
But the important consideration here is that if young women have already been exposed to these two most popular strains, the vaccine has no effect. In fact, some early testing has suggested that women who take Gardasil who are already infected with HPV are more susceptible to developing the lesions that lead to cervical cancer.
So the plan is to inoculate girls as young as possible, before they've had sex, hence the U.S. Food and Drug Administration decision to allow the drug on girls as young as nine, or when they are in Grade 4.
Not surprisingly, perhaps, the suggestion that grade-school aged girls be inoculated has caused a stir among social conservatives in the U.S. who argue that such a vaccine would only encourage promiscuity and a false sense of invulnerability to sexual disease.
The debate has been particularly heated in Texas. In March 2007, the Texas House of Representatives voted 119 to 21 in favour of rescinding Gov. Rick Perry's mandate to vaccinate sixth-grade girls with Gardasil.
The U.S. right is divided over the value of the vaccine: It appears to be popular among parents of young girls, according to surveys, and at least some religious groups are viewing it as a valid health response. In fact, social taboos in Third World countries may prove more powerful disincentives to breaking the back of cervical cancer, aid workers say.
That is why the Bill and Melinda Gates Foundation has given almost $28 million US to an international health group to try to figure out how to introduce a female-only HPV vaccine into socially-conservative countries like India, Uganda, Peru and Vietnam, where infection rates have been soaring and the prospect of many more women dying of cervical cancer in the years ahead is very real.
In fact, reaching these societies — and perhaps the broader male market in North America at the same time — may be the reason Merck included in Gardasil an extra vaccine against two other HPV strains that cause relatively harmless genital warts.
Merck says it did this because the wart strains can confuse HPV screening tests and cause unnecessary anxiety among patients. Some researchers, however, have said that this grouping will encourage men to get vaccinated to prevent disfiguring warts, and as a result they will no longer transmit the cancer-causing HPV strains to women.
According to the FDA., Gardasil is a safe and effective drug that proved effective 100 per cent of the time against its target strains. But while the drug has been in the works for almost 15 years — it appears to have originated in an Australian lab — it really only underwent formal testing over the past four years.
A report issued by the U.S. Centers for Disease Control in July 2008 found that 7,802 people who received Gardasil vaccines reported adverse reactions to the CDC's Vaccine Adverse Event Reporting System (VAERS) between June 8, 2006, and April 30, 2008. That's out of approximately 13.5 million doses that were given in the U.S. in 2006 and 2007. (The vaccine is usually given in three doses over six months.)
The CDC reported that the most common side-effect was pain at the injection site. Seven per cent of Gardasil recipients reported serious side effects — half the average for vaccines overall, according to the report. There were 31 reported cases of Guillain-Barré syndrome (GBS), a neurological condition that results in temporary but often total body paralysis, with 10 cases confirmed.
Fifteen deaths were also reported, with 10 of these containing the level of information required for further analysis, according to the CDC.
"After careful review of those reports, we could not establish the causal relationship between vaccination and death," reads the VAERS report.
On Aug. 19, 2009, another study of Gardasil side effects published in the JAMA found that the vaccine's safety record seems to be similar to that of other vaccines.
"For 23 million doses that have been sent out, we've received 12, 424 reports of adverse events," lead author Dr. Barbara Slade, who works for the CDC, said in a journal release.
The rates were comparable to those of other vaccines given to girls the same age at 54 reports per 100,000 doses given, the researchers said.
The team found 772 of the adverse events, or 6.2 per cent, were serious, including 32 deaths, as well as reports of anaphylaxis (severe allergic reaction), dangerous blood clots and nerve injury that can cause paralysis.
The Canada Vigilance Online Database, which tracks adverse drug reactions in this country, reports one adverse reaction involving a patient taking Gardasil, among other products, at the time of the reaction. The report says Gardasil was not suspected as the cause of her reaction, and she fully recovered.
Still, Gardasil is clearly part of the new frontier of cancer meds. It is the second of only two so-called cancer vaccines to have been approved in the U.S. though at least 14 others are in final, stage 3 trials. The first to be approved was a vaccine against hepatitis B, which is now part of an immunization program being used in all provinces, and which is said to guard against an infection that can sometimes lead to liver cancer.
Both it and Gardasil are considered prophylactic vaccines because they do not target cancers directly but rather the viruses that can lead to the disease.