The Gardasil HPV Vaccine: Not the Shot in the Arm Merck Hoped for

With the start of the school year, debate has heated up again about Gardasil, Merck's vaccine against human papillomavirus. Since writing my series of four articles on The Politics and PR of Cervical Cancer last year, I have continued to track the developments and have noticed some interesting trends. While Gardasil has not been the financial jackpot that Merck was hoping it would be, there is still a steady push for vaccination and even still for mandates. Even though it has not played out as positively as Merck planned, it is too early to turn our attention away from their efforts to sell their so-called "vaccine against cancer." Merck's obvious corporate steamrolling has generated a public backlash and has also faced general concerns about possible health risks from vaccinations, along with conservative opposition to the idea of government health mandates. These reactions slowed the company's money train but didn't bring it to a full stop.

The Drumbeat Goes On

The push for mandatory vaccination continues, and many of its supporters have received money from Merck, including Women in Government, about whom I wrote extensively in my article, "Women in Government: Merck's Trojan Horse." Despite a palpable turning of the tide against mandates, Women in Government still swims against the current. In a 2008 report titled "State of Cervical Cancer Prevention in America," WIG continued to push for mandates and gave higher scores to states that have introduced or passed legislation for this purpose.

WIG reports that 27 states, plus the District of Columbia, saw legislation introduced in 2007 that would have mandated HPV vaccination. To date, Virginia and the District of Columbia are the only places where the mandate has passed. In Virginia, it is already the law, but because it went into effect after the start of the current school year, the mandate's impact will not really be felt until Fall 2009. In DC, it needs Congressional approval to take effect. In the other states, legislation either died in committee, was referred on to the next legislation session, was withdrawn, or was modified to focus on education and availability of funds instead of the mandate.

Merck continues to promote Gardasil through advertising and PR. Building on the "One Less" ad campaign, designed and implemented by the Edelman public relations company, Merck is now pushing Gardasil in a series of "I Chose" commercials. The spots include adult women saying "I chose to get my daughter vaccinated because I want her to be one less woman affected by cervical cancer," while a girl intones "I chose to get vaccinated after my doctor told me Gardasil does more than help prevent cervical cancer." Again playing on parents' desires to protect their children and girls' needs to feel independent and empowered, the ad ends with a montage of women and girls saying "O-n-e-l-e-s-s. One less. Gardasil." In the end, women are told " "You have the power to choose. Ask your daughter's doctor about Gardasil."

The New Jersey Star Ledger reported on June 5, 2008 that Merck bought a 60-second ad slot to be screened before the blockbuster film, "Sex and the City" -- a long-awaited "chick flick" that gave Merck the perfect demographic for selling its vaccine. According to the Ledger, Merck's "research showed 76 percent of young women between the ages of 19 and 26 described advertising they saw before a movie as entertaining. But here's the clincher: The same young women said they pay more attention to ads on a movie screen than on television." This age range corresponds exactly to the target market for Gardasil, since 26 is the top age at which the U.S. Food and Drug Administration has approved giving the shots to women.

Recent Developments

Despite its corner on the market, Merck is not making as much on Gardasil as previously planned. Forbes reported on September 12, 2008 that "Merck has already scaled back full-year sales estimates for Gardasil from between $1.9 billion and $2.1 billion to between $1.4 billion and $1.6 billion, following regulatory setbacks and challenges making inroads with young adult patients." The company also suffered another financial setback: after initially insisting that it would never settle personal injury claims related to Vioxx deaths, Merck did just that to the tune of $4.85 billion. People injured by the painkiller are not the only ones who want Merck to pay up. Merck investors are also seeking class action status for a Vioxx-related suit against the company. Merck was initially successful in getting that claim dismissed, but the Wall Street Journal reported last week that the Third U.S. Circuit Court of Appeals has reversed that ruling.

Despite these setbacks, Merck continues to profit from Gardasil's monopoly status as the only FDA-approved vaccine for HPV on the market. It appears that they will have the market cornered longer than previously expected. GlaxoSmithKline's competing vaccine, Cervarix, was submitted to the FDA in March 2007 but has not yet been approved. Instead, the agency sent GSK a Complete Response Letter in December, 2007 asking for more information. GSK did not publicize the specifics of the letter, so analysts were left to wonder what the FDA wanted, and whether it would mean a short or long delay to approval.

In June 2008 GSK announced that they had provided follow up information to the FDA in response to the December letter, but they also made clear that there were tests in progress whose results they felt were critical to FDA approval. A June 30, 2008 GSK press release states that "'Study 008 is a key study that will be completing later this year, and we expect the final results will strengthen the U.S. label for Cervarix,' said Barbara Howe, M.D., Vice President and Director, North American Vaccine Development, GlaxoSmithKline. 'We continue to have positive and productive discussions with the FDA and remain confident in the vaccine's safety and efficacy profile. We look forward to bringing this important new cervical cancer vaccine to girls and women in the U.S.'" Those tests are scheduled to run through 2008, which means that GSK will not submit its findings to the FDA until early 2009, after which another six months at least will be needed before the FDA can make a decision on approval. Merck can therefore count on having the only dog in the fight for at least one more year.

Merck would like to expand vaccination with Gardasil to much older women, but even if the FDA approved it, there are serious cost-benefit questions.Merck has suffered a regulatory setback of its owh this year, when the FDA rejected its application to legally extend the ages for which Gardasil can be marketed. Currently, it is approved for girls and women between the ages of 9 to 26. Merck wanted to extend that to age 45, and initial reports said Merck had data to support the extension that they would submit to the FDA by the end of this summer.

August, however, saw a flurry of news stories and medical journal articles that cast serious doubt on the efficacy and cost-effectiveness of vaccinating women later in life. The August 21, 2008 issue of the New England Journal of Medicine (NEJM) carried both an editorial and a lengthy study on HPV vaccines. The editorial was written by Dr. Charlotte J. Haug, editor of The Journal of the Norwegian Medical Association. She directly challenged the claim that HPV vaccination is effective at preventing cervical cancer. "Despite great expectations and promising results of clinical trials, we still lack sufficient evidence of an effective vaccine against cervical cancer," she wrote. "With so many essential questions still unanswered, there is good reason to be cautious."

The accompanying NEJM study, "Health and Economic Implications of HPV Vaccination in the United States," looks specifically at the cost-effectiveness of the HPV vaccine. Anytime someone raises the question of cost-effectiveness, of course, someone is bound to object that we can't put a price tag on human life. In reality, however, cost-benefit considerations always play a role in health decisions. With respect to cervical cancer in particular, the high cost of Gardasil compares poorly against simple Pap smears, which provide a time-tested, reliable and inexpensive diagnostic tool that can detect premalignant processes early and thereby prevent cervical cancer. It seems, therefore, that financial and public health sense should favor programs to ensure that all women, but especially those most at risk from cervical cancer, receive consistent and appropriate screening.

As for Gardasil, the NEJM study concluded that while the cost benefit of vaccinating twelve-year old girls falls within accepted guidelines for wealthy countries, the cost benefit declines rapidly as age increases. This finding is a major blow to Merck's efforts to promote intensive "catch up" vaccinations of girls and women who are over the age targeted by schools and proposed mandates. The benefit drops dramatically by the time women reach the maximum approved vaccination age of 26. In the even higher age range of 27 to 45 for which Merck is seeking additional approval, the calculated cost benefit is far outside the accepted range.

This information might seem to suggest that it is all the more important to vaccinate girls at the youngest age possible. Merck's Dr. Richard Haupt told the New York Times that the NEJM study "underscores the value of vaccinating pre-adolescent girls." But there is a big hitch. The NEJM study states clearly that its cost-benefit ratios are based on an assumption that the vaccine provides lifetime immunity to HPV. There is no evidence that this is actually the case. In fact, a number of indicators suggest one or more boosters will be needed during the recipients' lifetimes.

Even in the best-case scenario, HPV vaccines would only prevent 70% of cervical cancer cases, which means that regular and consistent screening, such as tried and true Pap smears, will remain critical for women's protection against cervical cancer. This means that the significant costs of the three shot initial Gardasil vaccination series (with a price tag of $450-$1,000, not including a possible booster) will be in addition to the existing costs of screening.

The NEJM article spelled out the bottom line: "If vaccine-induced immunity lasted only ten years, the vaccination of preadolescent girls provide only 2% marginal improvement in the reduction of the risk of cervical cancer as compared with screening alone." Experts closely involved in drug trials for both Cervarix and Gardasil, such as Dr. Diane Harper, feel that immunity is likely to decline after as few as five years.

On August 21, 2008 the New York Times published an article titled "Researchers Question Wide Use of HPV Vaccines," which quoted extensively from the NEJM. The Times article emphasized a key point: Since cervical cancer grows slowly (often a decade from infection to full-blown cancer), there is no hard evidence yet that an HPV vaccine will actually lower the rate of cervical cancer. The vaccines can prevent some HPV infections that may lead eventually to cervical cancer if not diagnosed and treated. However, the tests have not lasted long enough yet to say definitively that the result will actually translate into a real decrease in cervical cancer. Evidence of real benefit therefore won't be available until enough years have passed that girls who receive the vaccine can be compaired against those who don't as they pass into adulthood and beyond.

That is quite a bombshell, and certainly a different message than Merck's marketing blitz has encouraged the public to embrace. Merck and its supporters would have you believe that time is of the essence and that society must move quickly to ensure that every young girl gets vaccinated. The main beneficiary of this hurry-up approach is Merck, not women and girls.

Things to Watch For

There are some likely developments on the horizon that I expect to emerge. One is that on September 12, 2008, Gardasil was approved by the FDA to carry labeling that it is also effective in preventing vaginal and vulvar cancer. According to the National Cancer Institute, the U.S. sees 5,670 cases of these types of cancer per year, causing 1,630 deaths. These numbers are much smaller than the figures for cervical cancer, which itself doesn't even crack the top ten fatal cancers for women. Nevertheless, we can expect more PR and advertising from Merck, aimed at "educating" us about the risk that they pose, however small they are in reality compared to other threats. (For comparison's sake, cancer of all types combined kills more than 500,000 people in the United States each year, while heart disease claims more than two million lives. An estimated 27,000 to 55,000 people have died just from taking Merck's Vioxx.)

Merck is also eager to get Gardasil approved for vaccinating boys. Why limit your potential market to just half of the population when you can ultimately target everyone? This may be a harder sell than they expect, but I would be surprised if they don't give it their best shot. HPV is implicated in some cases of penile and anal cancer, but neither is widespread in the United States. According to the National Cancer Institute, there are 6,320 cases of these types of cancer per year in the U.S., causing 970 deaths. These numbers do not suggest that the vaccine's benefit to male health is much of a selling point. Merck may try to sell men on the idea of getting vaccinated to avoid passing HPV on to their sexual partners, but altruism can be a tough sell, especially when it involves a painful series of shots and a high price tag. Only time will tell if Merck can successfully finesse the marketing.

Merck isn't the only company that stands to profit from continued interest in and worry about HPV. We haven't heard much from Digene, the makers of the HPV test, but I wouldn't be surprised if they ramped up their outreach as well. Especially with Gardasil not being approved for older women, Digene could try to market their test as a way to protect yourself even if you are too old to get the HPV vaccine. And of course, GSK will be hoping to get Cervarix approved in the U.S. as it has already done in many other countries worldwide.

Conclusion

With the amount of money to be made in this area worldwide, there is no chance of this issue disappearing anytime soon. There is no doubt that the development of an HPV vaccine could have and should have been cause for celebration -- advances in women's health care are truly few and far between. However, Merck's own overly aggressive PR campaign, its deceit in pushing for mandates through a non-profit front, and its willingness to over-hype its product has made it impossible for many of us to willingly embracing their so-called "vaccine against cancer."

If you'd like to read more on this issue, much of the material mentioned here came from a chapter that I contributed to a forthcoming book published by Project Censored. You can learn more about Project Censored and order the book at http://www.projectcensored.org/

The debate over Gardasil in Canada provides an interesting comparison to the debate in the United States. I was one of three guests on the Canadian Broadcasting Company's Sunday Edition program on September 7, 2008. Since Canada has a national health system, there are some differences in how this has played out, but there are also many similarities. One that is very reminiscent of the case in Texas in 2007, the federal Canadian government approval CA$300 million for provinces to access in order to implement mass HPV vaccination programs. What came out soon after was that only one short month before Stephen Harper's government put this plan into place, one of his former senior advisor has registered as a lobbyist for Merck. To make it even more questionable, the federal government put a time limit on how long the pool of money was available. In year one, three provinces bought in. In this, the second and last year of the offer, three more joined their ranks, but not without heated debate. That interview is available at http://www.cbc.ca/thesundayedition/ (If it has been moved from the front page, it is the September 7, 2008 program.)