Positive results for Gardasil trial in males

News came from Merck last week that results from its clinical trial of Gardasil in males showed the vaccine's efficacy in preventing HPV-related genital warts and other lesions. No serious safety concerns were found. Here's coverage from the Associated Press and the Merck press release detailing the (as yet unpublished) results which were presented at this European conference last week.

The trial included nearly 4,000 males between the ages of 16 and 26. The vaccine was 90% effective at preventing external genital lesions, the most common of which are genital warts.

Dr. Bernadine Healy, in the news earlier this year for comments seen as supporting a possible link between vaccines and autism, was pleased by these research results about Gardasil, writing about the many benefits of vaccinating males against HPV.

These findings will be part of Merck's eventual application to the FDA to license the vaccine for use in males in addition to females, a decision that has been widely expected for some time.

More interesting, however, will be the decision faced by the Advisory Committee on Immunization Practices regarding its recommendation for Gardasil in males. In particular, it remains to be seen if the direct protection provided against genital warts in males will be sufficient to recommend broad use of the vaccine, and/or what role the indirect benefits of male vaccination (i.e., aiding in the prevention of HPV-related disease in women) will play in the ACIP's recommendation.

No timetable has been set for these actions, but they are sure to be in the news in 2009.

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One other item related to HPV vaccines: The November 15 supplement to the journal Cancer is titled, "Assessing the Burden of HPV-Associated Cancers in the United States". It has a number of papers examining the burden of cervical cancer and other HPV-related conditions as well as several papers on the potential impact of HPV vaccination programs. Very interesting reading.

HPV Roundup: Gardasil safety worries, Cervarix FDA delays, more on mandates

There's been a flurry of media coverage this week about possible safety issues related to Gardasil. It appears that the attention was initiated by this report released by Judicial Watch, the conservative watchdog group. Like its previous reports alleging numerous deaths and illnesses caused by vaccine, this Judicial Watch report is based on unconfirmed submissions to VAERS, the government's clearinghouse for reports of possible vaccine-related adverse events. Reports to VAERS -- widely described as a 'hypothesis-generating mechanism' -- are later examined by government officials to determine what, if any, role a vaccine may have had in the reported condition.

Numerous other outlets have raised questions about Gardasil's safety in the past few days, most notably this CBS News story by Sharyl Attkinson, the media member who is increasingly at the forefront of reporting on alleged vaccine risks. Other media outlets examining the topic include CNN and WebMD.

In the meantime, officials from CDC and FDA have assured the public that the vaccine remains safe and effective and that reports of possible adverse events will continue to be investigated. Merck responded similarly yesterday, noting the limitations of reports made to VAERS.

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Meanwhile, it appears that the U.S. head-to-head battle between Gardasil and GSK's Cervarix will most likely be delayed until late 2009. Last week, the Wall Street Journal and Reuters, among others, reported the GSK announcement of its timetable for submitting additional trial data requested by FDA. Here is the GSK press release. It notes that Cervarix is already approved in 67 countries, including the E.U., but it's no secret that the U.S. market is by far the most lucrative, as Merck's sales figures from earlier this year illustrated.

From a business standpoint, this is decidedly good news for Merck, as it extends its head start in the U.S. (The news has not all been good, however, as it was announced late last month that Merck's application to expand the indication for Gardasil for women through age 45 will face additional scrutiny and delays. Here's a story from Reuters and the Merck press release.)

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In other news, two papers have recently been published in academic journals on HPV mandates (joining a growing literature on this topic -- including papers by Schwartz, et al., Colgrove, and Zimmerman.) One paper, "Assessing Mandatory HPV Vaccination: Who Should Call the Shots?" (Javitt, et al.) appears in the Summer 2008 issue of the Journal of Law, Medicine & Ethics (subscription required). In short, the authors conclude, "...Mandating HPV vaccination at the present time would be premature and ill-advised."

Also, the May 2008 Harvard Law Review published a paper titled "Toward a 21st Century Jacobson v. Massachusetts (pdf), alluding to the 1905 case that is widely seen as the foundation for state public health powers. The authors argue that a distinction should be drawn between vaccines that are 'medically necessary' (such as smallpox) and those that are 'practically necessary' (such as hepatitis B and HPV, for which other preventive measures are available but not widely used). The paper suggests that current law and policy fail to acknowledge the implications of this distinction.

Gardasil, RotaTeq sales top Merck quarterly report

As we've written previously, corporate financial reports aren't exactly our forte. However, the price of Gardasil (and, to a lesser extent, RotaTeq) have been prominent in policy discussions both in the U.S. and internationally, so this week's sales news from Merck is worth noting here.

This Merck document includes a table listing sales for various vaccines in the third quarter of 2007. Among the highlights:

• Gardasil: $418 million in sales
  
• RotaTeq: $171 million in sales
  
• Zostavax: $61 million in sales
  
• All other vaccines: $593 million in sales
  

Remembering that these numbers represent only three months of sales, we can see clearly that the days in which vaccines were not thought of as potential profit centers for the pharmaceutical industry are long over. (Moreover, most European vaccine sales are not included in these figures, making the true totals even higher.)

Here's coverage from Reuters and the Associated Press, which reports that total Gardasil sales for the first 9 months of 2007 is $1.14 billion. Also of interest is the detailed news release from Merck. According to is, Gardasil has now been approved in 86 countries (with 50 more pending) and RotaTeq is approved in 69 countries.

There's no doubt that many hope that these remarkable sales figures is the U.S. and elsewhere will encourage Merck to expand its programs (like this one) to deliver free or low-cost vaccines to those parts of the world that would benefit most from them.

"Most promising" HIV vaccine trial stopped; vaccine not effective

In what a colleague at Penn--an HIV researcher--describes as "very big and very disappointing news", Merck announced Friday that it was halting clinical trials on what was viewed as a highly promising HIV vaccine candidate, the most advanced vaccine that employed a new strategy attempting to stimulate T-cell immunity against the virus. An interim analysis of research data found that the vaccine was not effective.

Here's the front page story from Saturday's New York Times -- Failure of Vaccine Test is Setback in AIDS Fight, and more coverage from Scientific American, The Associated Press, and The Washington Post. Here are official statements from Merck, NIH, and IAVI.

Also of note is this editorial in today's Philadelphia Inquirer, "Starting fresh for an HIV vaccine."

More good news on Gardasil cross-protection?

An Associated Press story published last week began with what seemed to be remarkable news:

"New data show that a vaccine against the virus that causes cervical cancer partially blocks infection by 10 strains of the virus on top of the four types targeted. That boosts protection - at least partially - to 90 percent of strains causing the deadly cancer, according to data presented yesterday at a medical conference by Merck & Co., maker of Gardasil."

90% protection? Recalling that 70% had long been the number used to quantify the percentage of cervical cancer-causing HPV strains covered by the vaccine, this would be a major development.

As is often the case with unpublished data presented at medical conferences, specifics on the research results are difficult to come by. However, this WebMD story published at CBSNews.com adds more detail, explaining, "The new study, which involved about 11,000 young women aged 15 to 26, shows that the vaccine is also 38% effective against 10 additional HPV types, which are responsible for an additional 20% of cervical cancers."

The fact that the vaccine is only 38% effective against these additional strains is never clearly stated in the AP story. (Research has shown the vaccine to be 100% effective against the 70% of cancer-causing strains included in the vaccine.)

The findings are still good news, but readers of the AP story -- published in our hometown Philadelphia Inquirer and no doubt many other newspapers -- could be excused for thinking it was even more noteworthy.

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In other Gardasil news, Merck announced today plans to donate 3 million doses of the vaccine for use in the developing world. Here's coverage from the Associated Press and a Merck press release.

Merck report: $358m in Gardasil sales for Q2; $1 billion total for vaccines

While we don't typically highlight corporate earnings reports or similar news, the quarterly report released Monday by Merck for April-June 2007 provides some new information about the growing market for vaccines, and, in particular, Gardasil. Here's coverage from yesterday's New York Times, "Another Quarter of Strong Results by Merck," and a similar story from Reuters.

Since this news comes directly from the company, the Merck press release is particularly useful. Here's part of what it says about vaccines:

"Total vaccine sales, as recorded by Merck, were $1.0 billion for the quarter, compared to $349 million in the second quarter of 2006. The growth in vaccine sales was led by the performance of GARDASIL along with strong contributions from ROTATEQ and other pediatric vaccines. Vaccines in most major European markets are sold through the Company’s joint venture, Sanofi Pasteur MSD, and the results from its interest in the joint venture are recorded in equity income from affiliates.

Total sales as recorded by Merck for GARDASIL, the Company's cervical cancer vaccine, were $358 million for the second quarter. As of the second quarter, GARDASIL has been approved in 80 countries, many under fast-track or expedited review; and launched in 59 of those countries. The vaccine remains under review in approximately 40 other countries.

ROTATEQ, Merck's vaccine to help protect children against rotavirus gastroenteritis, achieved worldwide sales, as recorded by Merck, of $119 million for the quarter. As of the second quarter, ROTATEQ has been approved in 61 countries and it has launched in 22 of those countries."

The release goes on to note sales figures for Proquad ($89 million), Varivax ($147 million), and Zostavax ($47 million).

A companion document released by Merck breaks down sales between the U.S. market and internationally. Nearly 80% of Gardasil sales were in the U.S. ($286 million), as were an amazing 96% of RotaTeq sales ($114 million). There's little doubt from these data that the U.S. is leading the way in the uptake of these two fairly new vaccines, despite the far greater need for cervical cancer and rotavirus prevention internationally.

Overall, $1 billion in vaccine sales for a single company in a three-month period is perhaps the best evidence to date of the potential profitability of vaccines to an extent not previously seen. As for Gardasil, it is difficult to work backwards from the sales figures given ($358m) to ascertain the number of doses sold during the April-June period, since governments and insurance companies pay less than the well-known $120/dose 'sticker price'. This CDC price list shows a cost of $96.75/dose for Gardasil as part of the Vaccines for Children program. Using those figures as endpoints, a very rough estimate would suggest 3-4 million doses were sold, or enough doses to fully vaccinate slightly more than 1 million girls.

Given the size of the population for whom vaccination is recommended (all females 11-26), the potential growth of the Gardasil market is staggering, perhaps explaining, in part, the company's apparent enthusiasm to promote its vaccine in advance of the arrival of GSK's Cervarix.

From Pediatrics: GSK rotavirus trials; trial of school-based flu vaccine program

In a slow midsummer period for vaccine news, two papers appearing in the journal Pediatrics this month deserve mention:

• "Dose Response and Efficacy of a Live, Attenuated Human Rotavirus Vaccine in Mexican Infants" -- This is a report on a trial of GSK's rotavirus vaccine, Rotarix. The study of 405 infants showed the vaccine to be safe and effective. Rotarix is still awaiting U.S. licensure -- the application was filed late last month, according to this announcement -- but it is already available around the world (including the EU, as this 2006 press release announced). With Merck's rotavirus vaccine, RotaTeq, available in the U.S. since 2006, another Merck-GSK head-to-head showdown is bound to occur, albeit one certain to be far less noticeable than the imminent competition for the HPV vaccine market likely to begin in 2008.

• "Mass Distribution of Free, Intranasally Administered Influenza Vaccine in a Public School System" -- The paper reports on a school-based influenza vaccination program in the Knoxville, TN area. Roughly 24,000 of 53,000 students received the FluMist vaccine, an encouraging number according to the study's authors. Of concern, however, was the amount of resources (notably, 6900 person-hours of labor) needed to execute the program. The program described here was funded in part by MedImmune (since purchased by AstraZeneca), the manufacturer of FluMist. Nevertheless, the paper's authors are correct to note the value of trials such as this in evaluating the feasibility of school-based programs to increase pediatric vaccination rates or as part of pandemic response efforts.
  

Info on Kawasaki disease added to RotaTeq label

A colleague from CDC alerted us to this announcement regarding a change to the label of RotaTeq, Merck's rotavirus vaccine recommended to all infants at 2, 4, and 6 months. Here's the first paragraph of the CDC statement:

"The Food and Drug Administration (FDA) approved today a revised label for RotaTeq, a rotavirus vaccine manufactured by Merck and Co., Inc., to include information on reports of Kawasaki disease occurring before and after the vaccine’s licensure in February 2006. FDA has not made any changes to its indications for use of RotaTeq nor has it issued new or revised warnings or precautions. Likewise, the Centers for Disease Control and Prevention (CDC) has not made any changes in its recommendations regarding the use of RotaTeq. Healthcare providers and parents should remain confident in using RotaTeq in infants."

Here's the FDA release and a related story from Reuters (the only media outlet to have reported on this item as of now.)

General info on Kawasaki disease can be found here and here. It's a rare and poorly understood inflammatory condition that affects 4,000 American children annually.

The "label" referred to in the announcements above is actually this document, an 11-page, single-spaced, data-laden product insert unlikely to top the reading lists of most parents (or pediatricians, for that matter).

The FDA statement notes, "The cases reported to date are not more frequent than what could be expected to occur by coincidence," a statement that could also describe its announcement in February regarding intussusception reports among recipients of RotaTeq.

Similar to that earlier occasion, this announcement was seemingly made so that providers and parents may be vigilant in looking for symptoms of Kawasaki disease, in case a connection to the vaccine does exist. However, calling attention to severe conditions for which no evidence suggests a vaccine link may create undue confusion and worry among parents still told to vaccinate their children with RotaTeq. Admittedly, it is a difficult balance that must be weighed by policy-makers, but one that merits further study.

More Benefits of Gardasil?

With GSK's HPV vaccine -- Cervarix -- about to enter the final stages of FDA review prior to its all but certain licensure in the coming months, the marketing battle between GSK and Merck is about to begin in earnest.

One precursor of what's to come has been the occasional announcements and published papers noting protection against additional HPV strains beyond those specifically included in the vaccine. We've linked to many of those items previously.

Another sign is this headline: "Gardasil Guards Against Vaginal, Vulval Cancers: Researchers found cervical cancer vaccine reduced risk of lesions by 49%". The story is based on a paper in the latest issue of The Lancet by Joura and colleagues (abstract available here with free registration).

Gardasil: Recommendations published, views on industry role, male vaccination, N.M. mandate, and more

Some updates from the past 10 days or so on recent news about Gardasil and the ongoing discussions about mandates...

• Last Monday, the official ACIP recommendations on Gardasil were published online in MMWR. These are essentially the same recommendations that were announced in June 2006 (which we first wrote about here) -- there is an increasingly longer lag between such announcements and publication in MMWR. One important consequence of publication is that it typically pressures insurance companies who have not yet agreed to cover the cost of the vaccine to do so.

• A story in today's Detroit Free Press asks, "Why aren't more girls getting HPV vaccine?" The story relies more on anecdotal reports than any real data, however. The two million doses of Gardasil shipped in the 9 months since licensure is a not-insignificant number, particularly considering the delays in insurance coverage in many cases. Nevertheless, it may be a question worth asking. This AP story may be relevant to the discussion, examining continued public ignorance about HPV, despite the attention it's received in the past year.
  

• An interesting (and provocative) opinion from Adrian Fugh-Berman on "Bioethics Forum" (the blog of the Hastings Center, the bioethics think-tank) -- "Cervical Cancer Vaccines and Industry Influence". Fugh-Berman's conclusion: "Cervical cancer is uncommon in the United States. This is not an emergency; this is not SARS. Listen only to public health people without conflicts of interest. There’s time for a discussion – but ban industry from the room in which any decisions on public health are made." Worth reading, regardless of one's own opinion on the topic.
  

• Following up on our colleague James Colgrove's perspective on HPV mandates in NEJM last fall (which we noted then), several letters to the editor were published earlier this month in response. One letter highlights the potential value of vaccinating males, and another takes issue with the use of the word "compulsory" to describe vaccination requirements that allow for informed refusal. This point goes to the increasing use of the term "opt-out requirement" when discussing what have traditional been known as state mandates.

• Speaking of vaccinating males, yesterday's Los Angeles Times took a closer look at some of the unique issues regarding HPV infection in men and the potential value of vaccination.
  

• New Mexico appears to be the next state on the verge of an HPV school-entry requirement. Here's a story from last week about the passage of a bill in its state legislature. As best as we can tell, the bill is still awaiting Gov. Bill Richardson's signature, which could happen at any time. Many other states -- too many to count -- have bills at some stage of the legislative process.

• The Powerpoint slides from last month's ACIP meeting were recently posted here. Updated Gardasil efficacy data from Merck's Eliav Barr are available there, as is a general overview of the American HPV vaccine landscape by CDC's Lauri Markowitz. It's very interesting for those looking for somewhat less-filtered information than what appears in the popular media.

Gardasil round-up: Merck lobbying, ACIP chair comments, Virginia mandate, and more

There continues to be a steady trickle of news about Gardasil, largely centered on the ongoing debate regarding possible state mandates. Rather than attempt to keep up with each day's new op-eds, news stories, and the rest, we've decided to combine several of the most interesting items from the past 10-14 days into a single post. With that, here are some recent items making headlines:

• Perhaps the biggest news from the past few weeks was Merck's decision to stop participating in lobbying efforts for state mandates. Here's one account of the story from late February, courtesy of Reuters. It quotes Merck's Richard Haupt calling the company's activities a "potential distraction." Few would disagree with this assessment, and it is surprising, given the company's extensive and seemingly well orchestrated marketing and education efforts, that it would commit so significant a public relations blunder.

• Since that announcement, there has been no shortage of stories and op-eds more or less making the same point, namely, that the Texas political controversy and Merck's lobbying efforts have obscured the scientific and medical aspects of the vaccine and its potential benefits. That's the thesis of this New York Times editorial, "A Necessary Vaccine," (subscription required) which generated a number of letters in response. Also: a story in today's Times titled "A Vital Discussion, Clouded."

• Sunday's Washington Post also looked at these issues ("Parents Question HPV Vaccine: Push to Mandate Shots Rapidly Creates Backlash") Quoted in this story is ACIP chair Dr. Jon Abramson, who makes clear here and elsewhere that he is no supporter of current attempts to mandate vaccination. Abramson is also featured in this essay by Arthur Allen, "Why It's Too Soon for a Mandatory HPV Vaccine," published in the New Republic Online.

• Also mentioned in the Washington Post story above is the imminent action by Virginia Gov. Tim Kaine to sign legislation making his state the second to mandate HPV vaccination. The requirement would not take effect until 2008 or 2009 and would include the traditional types of exemptions (increasingly referred to in the media, accurately, as an 'opt-out provision'.) More information can be found in this story.
  

Potential supply issues for varicella-containing vaccines

Late last month, the CDC's MMWR included a "Notice to Readers" titled "Supply of Vaccines Containing Varicella-Zoster Virus." What are those vaccines? Varivax (against chickenpox), Zostavax (against shingles), and Proquad (a combination of MMR and chickenpox). All are manufactured by Merck, and no other U.S. companies manufacture vaccines providing protection against VZV.

There's no shortage to report, only news from Merck that the yield produced from early stages of the vaccine manufacturing process are less than expected (the reasons for which are not yet known). In the meantime, the plan is to prioritize production of the chickenpox and shingles vaccines, creating the potential for a limited supply of the combination ProQuad by late 2007. Again, not a major issue, as children can receive the same protection by receiving MMR and Varivax separately.

However, this announcement does remind us of the potential fragility of the U.S. vaccine supply. In addition to varicella-containing vaccines, those against measles, mumps, rubella, HPV, and rotavirus, among others, are all produced by a single manufacturer in the U.S. While the economic reasons behind this single-supplier market have been discussed by many, minor hiccups such as this announcement raise the attention of those who worry that the system is not sufficiently insulated against the risk, however small, of major production problems affecting a recommended vaccine.

More on Texas HPV vaccine mandate backlash

There continues to be a tremendous amount of coverage of Gardasil in the media, most of it focused on reaction to Texas Gov. Rick Perry's nearly-three-week-old executive order rather than the vaccine itself, HPV, or cervical cancer.

Saturday's New York Times wrote about the "Furor on Rush to Require Cervical Cancer Vaccine." The story's premise:

"But a roaring backlash has some health experts worried that the proponents, including the vaccine's maker, Merck, have pushed too far too fast, potentially undermining eventual prospects for the broadest possible immunization."

Syndicated columnist Clarence Page writes, "Don't judge cancer vaccine by Austin political fallout," attempting to encourage the public to distinguish the political controversy created by Perry's actions from the merits and potential benefits of the vaccine itself. He argues,

"With emotions heated up, a lot of misinformation and unnecessary anxieties already are being stirred up over the new vaccine. The least grounded appears to be the fear that it will encourage more sexual activity outside marriage. Our society unfortunately has many larger reasons for that and it is a worthy debate for another time.

For now, Gardasil appears to be a very important and welcome life-saving step forward in the fight against cancer. Don't judge it by the political confusion it has caused."

For an example of emotions heated up, take a glance at this political cartoon at Newstarget.com.

A few more op-eds of note: In Newsday, Marc Siegel writes in favor of broad vaccination (though not explicitly addressing the question of mandates). In the Atlanta Journal-Constitution, Former Rep. Bob Barr writes against mandates, in part:

"None of these concerns will likely deter the legion of Big Government types out there who — allied with the many do-gooders populating state legislatures from California to New York, and prodded by companies willing to spend millions to make billions — will allow nothing to stand in the way of 'good government,' whether the people want it or not."

As far as news goes, the latest in Texas is an effort in the state legislature to effectively reverse Perry's executive order. According to this story, a hearing on the topic yesterday went well into the night. The Houston Chronicle has more.

Finally, the Arts and Leisure section of Sunday's New York Times took a closer look at the visual and creative elements of Merck's "One Less" television commercial.

Renewed attention to possible rotavirus vaccine link to intussusception

A fairly significant amount of alarm was raised by an FDA statement last week titled "Information on RotaTeq and Intussusception". The statement reports 28 cases of intussusception -- the significant intestinal complication that led to the removal of the first rotavirus vaccine, RotaShield, in 1998 -- in children following administration of RotaTeq.

But what may have seemed at first glance to be a major announcement about the vaccine's safety was clarified later in the statement...

"Intussusception can occur spontaneously in the absence of vaccination. Of the reported 28 cases of intussusception, the number that may have been caused by the vaccine, or occurred by coincidence, is unknown."

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"The number of intussusception cases reported to date after RotaTeq administration does not exceed the number expected based on background rates of 18-43 per 100,000 per year for an unvaccinated population of children ages 6 to 35 weeks (CDC, unpublished data)."

In other words, there's no reason to be alarmed about the number of cases reported to date, but the statement, not unsurprisingly, did just that. This AP story by Andrew Bridges originally did not include any information about the background rate, likely contributing to the Alliance for Human Research Protection (and others, no doubt) misinterpreting the FDA item. "Merck rotavirus vaccine linked to 28 reports of life-threatening effect," is how the AHRP item describes the announcement, not at all what the FDA said.

CDC promptly released a statement attempting to clear up confusion. Among the 'key facts' they list:

• "We are not surprised by the number of reported intussusception cases following RotaTeq vaccination."
• "Intussusception, a form of bowel obstruction, occurs spontaneously in the absence of vaccination."
  
• "This notice does not mean there is a problem with the RotaTeq vaccine."

There's been no detectable coverage of this topic in the media since the initial FDA statement last week. It will, however, be discussed at this week's meeting of the ACIP, the agenda for which can be viewed here.

Texas HPV vaccine mandate in the news

There has been a great deal in the news this week about Gardasil (and a corresponding spike in our traffic), much of which has been triggered by Texas Gov. Rick Perry's executive order on Friday requiring sixth-grade girls to be vaccinated against HPV. Here's the text of the executive order and an accompanying press release from the governor's office. Quoting Perry, "Requiring young girls to get vaccinated before they come into contact with HPV is responsible health and fiscal policy that has the potential to significantly reduce cases of cervical cancer and mitigate future medical costs."

Perry, a Republican, has received criticism for this decision from members of his own political party and conservative organizations, as this AP story and this Houston Chronicle story explain. Perry released a second statement over the weekend, saying, in part,

"Providing the HPV vaccine doesn’t promote sexual promiscuity anymore than providing the Hepatitis B vaccine promotes drug use. If the medical community developed a vaccine for lung cancer, would the same critics oppose it claiming it would encourage smoking?

"Finally, parents need to know that they have the final decision about whether or not their daughter is vaccinated. I am a strong believer in protecting parental rights, which is why this executive order allows them to opt out."

Indeed, likely lost in the headlines pointing to a "mandate" is the important point that the exemption policies already in place in Texas will apply to HPV vaccination in the same way, including parents having the ability to decline vaccination for 'philosophical reasons'. In fact, proponents of vaccine mandates will likely be disappointed to learn that the executive order also instructs state officials to make the exemption process easier by creating a system in which parents can decline vaccination online.

Today's New York Times includes an editorial praising Perry for the decision. In fairness, it argues far more convincingly for HPV vaccination generally than it does for a state mandate (though strong arguments can certainly be made for it.)

Independent of discussions about the appropriateness of philosophical exemptions from vaccination (such as Paul Offit's op-ed we noted here), the current state mandate system means that no parents will be forced to vaccinate their children against their will. However, years of experience have shown that state mandates provide the structures and encouragement necessary to maximize a vaccine's benefit across communities, particularly reaching those without regular access to medical care whom cervical cancer targets disproportionately.

When considering vaccine mandates, we should not focus our attention on those with strong beliefs opposing vaccination, as the exemption procedures provide, for better or worse, a relatively simple remedy. Instead, we must consider those silent in these debates, those not receiving even basic medical care, much less tracking the minute-by-minute developments regarding Gardasil. For them, state mandates have been shown repeatedly to provide the awareness and stimulus needed for the vaccine to reach all who could benefit from it.

GSK planning head-to-head comparison of HPV vaccines

Earlier this month, GSK announced its plans to conduct a head-to-head clinical trial comparing its HPV vaccine, the still-unlicensed Cervarix, with Merck's Gardasil. Here's the GSK press release and a provocatively-headlined story from the Philadelphia Inquirer, "Area drug firms go to war over vaccine."

As the story notes, such a trial design is rare in medicine and all but unheard of for a vaccine. There's little doubt that this move by GSK is an attempt to frame an argument for the superiority of its HPV vaccine, despite the numerous advantages of Merck's Gardasil at present, among them, an increasingly longer head start in the market, immense media coverage over the past year, data showing 100% effectiveness (with respect to the HPV strains included in the vaccine), and the additional protection it provides against genital warts. Whatever their motives, head-to-head comparisons are helpful to patients and physicians, and it would by no means be a bad thing for other manufacturers of pharmaceuticals and vaccines alike to follow this lead, despite the high risks.

A sidebar piece in the same issue of the Inquirer looked at cost and access issues related to Gardasil. One interesting item: According to Merck's Richard Haupt, about $80 million worth of Gardasil had been sold through October, which he describes as "an extraordinary uptake." At Merck's listed price of $120/dose, that works out to roughly 660,000 doses, or enough to fully vaccinate 220,000 girls and women. (That number is likely higher, given the discounts offered to government programs and other groups).

Gardasil: Profile of Merck Vaccines president; feature on early HPV-cancer link proponent

Two items worth reading for those interested in background content related to Gardasil's development and arrival:

• "Making her mark at Merck" (Business Week, 8 January) -- A profile of Margaret McGlynn, the president of Merck Vaccines. An interesting item in the story: "Analysts are counting on McGlynn to drive much of Merck's growth: Some predict revenues from her division will triple by 2010, to $6 billion." While the business of vaccines is not our area of expertise, this is point underscores the period of explosive growth for vaccines that we're just entering, one in which ethical considerations will demand that much more attention.

• "Cancer quest: How ex-Penn scientist's hunch led to cervical vaccine" (Philadelphia Inquirer, 24 December) -- A very lengthy feature (two pages in the print edition) on
  Dr. Harald zur Hausen, described in the story as a very early proponent (i.e., the 1960s) of a link between HPV and cervical cancer (the credit for proving such a link has gone to others in the early 1980s). A very interesting, seemingly well researched piece.
  

Assessing pediatrician attitudes on rotavirus vaccine

The January issue of Pediatrics has a number of items discussing RotaTeq, Merck's rotavirus vaccine. Most interesting to this group is a paper titled "Will pediatricians adopt the new rotavirus vaccine?," a survey of attitudes among 431 physicians (free abstract, subscription required for full text). Much of the data was presented at the February 2006 ACIP meeting at which RotaTeq received a universal recommendation.

Here's a portion of the results section:

"Of the respondents, 52% strongly agreed and 37% somewhat agreed with the need for a rotavirus vaccine. If recommended for routine use, 50% would strongly recommend and 34% would recommend but not strongly; 52% would begin to use within 6 months and 27% from 6 months to 1 year. The top 3 "definite" barriers to implementation included concerns about uniform coverage of vaccine by insurers, lack of adequate reimbursement, and parental reluctance because of withdrawal of previous rotavirus vaccine."

Merck launches Gardasil ad campaign

Merck today announced the launch of a national advertising campaign for Gardasil. Information on the campaign, dubbed "One Less" (as in 'one less life affected by cervical cancer'), appears in this press release. The TV ads are available for viewing on the Gardasil website.

As the press release notes, this campaign follows earlier (and continuing) HPV education efforts supported by Merck, "Tell Someone" and "Make the Connection". Back in May, we wrote about some of the questions being raised by the company's "Tell Someone" campaign here (our most widely visited post in our 8-month history), particularly the omission of any reference to the then-still-unlicensed Gardasil. (Mentioning the vaccine in an ad before it was licensed would have violated FDA guidelines, but the ads still raised eyebrows among some.)

Regardless, the "One Less" campaign is unabashedly promoting Gardasil, as is entirely appropriate for Merck to do. From all appearances, if this isn't the first major national ad campaign for a vaccine, it will certainly be the largest by far, likely to supplement ads in medical journals (the traditional domain of vaccine advertisements) with those on television and other popular media. Yet another sign that the world of vaccines has entered a new, very different, and very promising phase in its history.

Speaking of Merck, there's a notable story in today's Times of Trenton from Dow Jones Newswires -- "Merck stakes its future on demand for vaccines." In yet another story explaining the growing importance of vaccine sales to pharmaceutical companies, there are some interesting facts about Gardasil's production facilities and plans. For example...

"In a plant that Merck expanded a few years ago while Gardasil was still being tested in clinical trials, three shifts of employees now work around the clock producing the vaccine. So far, at least 750,000 doses have been shipped since Gardasil's June launch, contributing to sales of more than $80 million so far."

Shingles vaccine recommended for adults 60+

We'd be remiss not to mention the biggest development out of this week's ACIP meeting, namely, the recommendation that all adults age 60 and over receive a single dose of Merck's new shingles vaccine, Zostavax. Here's the CDC press release, the Merck press release, and an AP story (courtesy of the Washington Post).

Also useful is this site assembled by the NIP with numerous resources about the painful condition formally known as herpes zoster and the new vaccine against it. Zostavax was licensed by the FDA in May and is the latest in a series of new vaccines introduced by Merck during the past year, though it's safe to say that this news hasn't received a hundredth of the attention that went to Gardasil in June.

ACIP: June minutes and October agenda

The folks at the Immunization Action Coalition pointed out that the full minutes from the June 2006 meeting of the CDC Advisory Committee on Immunization Practices are now available here. The 96-page PDF is the next best thing to attending the meeting yourself, as it provides comprehensive coverage of everything that took place. In June, of course, the major news was the recommendation vote for Merck's HPV vaccine, Gardasil. For those interested in the data that informed the ACIP's recommendation, the report is invaluable.

Also on the ACIP website is a draft agenda for the group's next meeting, scheduled for October 25-26. The most notable item is a scheduled vote on a recommendation for Merck's shingles vaccine, Zostavax, for use in adults.

Rotavirus inventors to receive CHOP gold medal

As this front-page story in today's Philadelphia Inquirer reports, the three researchers responsible for the discovery of what ultimately became Merck's new rotavirus vaccine, RotaTeq, will receive the "Gold Medal" from the Children's Hospital of Philadelphia. As even the brief outline in the Inquirer story suggests, the story of RotaTeq could be a case study for the difficulties of developing new vaccines -- the work leading to this year's FDA licensure and ACIP recommendation extends all the way back to research conducted in 1980.

Congratulations to Paul Offit, Stanley Plotkin, and Fred Clark on this latest honor. (For the record, Offit and Plotkin are friends and colleagues who have contributed their insights and expertise in various ways to the development of the Ethics of Vaccines Project.)

Should Gardasil be called a 'cancer vaccine'?

A few weeks back, we were asked by a reporter whether it was misleading to refer to Gardasil as a 'cancer vaccine'. The phrase has been widely used of late -- and not only by the media. Both the FDA and Merck refer to Gardasil as a 'cervical cancer vaccine' in their press releases this month announcing the product's licensure.

We hadn't thought much about the issue at the time, but it didn't (and still doesn't) strike us as dishonest. There's no dispute regarding the link between HPV and cervical cancer, and the data show that Gardasil prevents infection from HPV strains responsible for 70% of such cancers. The fact that the vaccine is less than 100% protective against cervical cancer has no impact on whether it can rightly be called a 'cervical cancer vaccine,' since no vaccine available provides complete protection.

Gardasil is beneficial for multiple reasons, but cervical cancer is clearly the most prominent of the group. From a medical perspective, referring to it as a cervical cancer vaccine is prudent, as public awareness of HPV (and, in particular, its close link to cancer) is lacking. A vaccine against cervical cancer is much more likely to attract patient interest than one against 'human papillomavirus,' meaning that more people who should receive the vaccine actually will. Meanwhile, there's no denying that the branding of Gardasil as a cervical cancer vaccine is a shrewd (but appropriate) marketing decision by Merck.

A story in today's Charleston (W.V.) Gazette is the first we've seen that discusses this topic. Most of those interviewed in the story appear to share our view, with the chief reservation being that the branding ignores the other benefits of vaccination. True, but the additional attention Gardasil receives as a 'cervical cancer vaccine' will likely put it in a better position to accomplish its full range of benefits for a greater number of people.

"Merck's vaccine victory not yet complete"

So notes a story on TheStreet.com, the financial news and opinion site, that looks ahead to this week's ACIP actions on Gardasil and subsequent decisions that will be made at the state level. We agree wholeheartedly with the gist of the story, particularly because it quotes at length an earlier post from this very site.

Gardasil approved -- $360 for 3-dose series

By no means surprising news, but Merck's HPV vaccine, Gardasil, was approved by the FDA earlier today. Here's the initial AP story, courtesy of the Washington Post, followed by the lengthy Merck press release which carries the triumphant headline, "FDA Approves Merck's GARDASIL, the World's First and Only Cervical Cancer Vaccine," a not-so-subtle jab at GSK in winning the race to be first with a licensed HPV vaccine. More importantly, the press release includes the first mention of Gardasil's 'catalog price': $120/dose, with 3 doses required for protection. The press release also announces the launch of www.gardasil.com, which (at least for now) only carries a "Coming Soon" banner.

We'll be watching for the arrival of the next phase of Merck's "Tell Someone" campaign (which we've previously discussed here and here) that will surely promote Gardasil, both in TV ads and on the websites that (so far) have made no mention of HPV vaccines.

Plenty of media coverage tomorrow, no doubt. We'll post some of the best here.

As expected, HPV vote tops June ACIP agenda

Prior to the Memorial Day weekend, the first (public) draft of the agenda for the June 29-30 meeting of the CDC Advisory Committee on Immunization Practices was released. As usual, a wide range of topics are slated to be covered in the two days, but attention will overwhelmingly be directed at the first item on the agenda, the recommendation vote for Merck's HPV vaccine, Gardasil. (Technically, this assumes FDA licensure early next month, but all signs suggest this is all but a sure thing.)

The expected ACIP actions next month follow nearly four hours of presentations and discussions on HPV vaccines at the group's last meeting in February. The minutes for that meeting recently surfaced on the ACIP website, and are well worth reading for those interested in data galore on all aspects of HPV vaccines -- from Merck and GSK's research data, to cost-effectiveness studies, to analyses of possible behavioral consequences of vaccination, and more.

It's worth repeating that while the ACIP recommendation is very significant, the ultimate decision as to whether HPV vaccination will be mandated as a condition of school attendance is the responsibility of each state. Since that appears to be the key point of contention for critics of the vaccine, the federal actions expected in the next month will likely only mark the start of months of deliberation, lobbying, and scrutiny centering on each state's department of health.

A final 'program note': we'll be in Atlanta for the meeting and will be posting extensively here on the discussions and decisions that take place.

More on Merck's "Tell Someone" HPV awareness program

Earlier this week, we wrote about the intriguing ad campaign launched by Merck to stress the link between HPV and cervical cancer. With the imminent arrival of the company's HPV vaccine, Gardasil, it seemed obvious that the print, TV, and web presence were the first steps in the rollout of promotion for Gardasil. Not so, says Merck, in this Bloomberg.com story:

"Gary Ruskin, executive director of Commercial Alert, a consumer group based in Portland, Oregon, that is critical of drug company advertising, said Merck's promotional Web site on the viral connection to cervical cancer is 'deceptive and dishonest.''

'Merck doesn't tell you why the site exists, which is to sell Gardasil,' Ruskin said.

[Kelley] Dougherty, the Merck spokeswoman, said the campaign isn't about Gardasil.

'This campaign is part of a broad and longstanding Merck public health commitment to encourage education about the disease,' Dougherty said in an e-mail."

Merck launches a costly, multi-platform ad campaign bringing attention to a virus for which the company just happens to have a vaccine set to arrive in the next month, and one has nothing to do with the other? More likely is that the spokesperson is trying to prevent Merck from running afoul of laws prohibiting advertising for medications (and vaccines) not yet approved for use in the U.S., a category that would include Gardasil -- at least until June 8.

That said, the Bloomberg story suggests that there is plenty of need for education about the link between HPV and cervical cancer. According to data from Merck, fewer than 20% of women in the U.S. are aware of the connection.

Health education is crucial, but many in the medical community continue to be wary of this responsibility falling to the pharmaceutical industry, whether through visits from drug reps, free meals, sponsored conferences or lectures, or direct-to-consumer advertising such as the "Tell Someone" campaign.

***Update: November 14, 2006 -- For more recent perspectives on Merck's "One Less" advertising campaign, click here.***

Merck's Gardasil moves one step closer to licensure

There's news this week about Merck's HPV vaccine, Gardasil. The headline is that an FDA committee, the Vaccines and Related Biological Products Advisory Committee, voted unanimously that Gardasil is safe and effective at preventing precancerous lesions in the cervix and genital warts caused by the four HPV subtypes included in the vaccine. The group recommends that the FDA license the vaccine, a decision expected to be made by June 8.

This news isn't much of a surprise, as the data for the vaccine's safety and effectiveness are clear. Also, it should be noted that this committee's findings are not binding, though the FDA's actions typically mirror such recommendations.

Here's an AP story on the announcement and Merck's news release. Also worth reading is this Boston Globe story, which highlights the need for continued cervical cancer screening and the ongoing debate over the benefits of vaccinating boys.

Lots of reaction pieces, including this one in the Los Angeles Times which quotes representatives from the Family Research Council and discusses the procedures for implementing state requirements for vaccination. This story on the Houston Chronicle's website includes reaction from Focus on the Family. Also, here's a statement from the president of Planned Parenthood.

(Those interested might want to explore our previous posts on HPV vaccines: here, here, here, here, here, here, here, here, here, and here.)

At least 5 years of protection from Merck HPV vaccine

A few weeks ago, we discussed the news from GSK that their cervical cancer vaccine, Cervarix, appears to provide at least 4.5 years of protection against the pre-cancerous lesions caused by HPV types included in the vaccine. Today, news from a conference in Paris that Merck's vaccine, Gardasil, offers at least 5 years of such protection. Reuters has the story.

We should expect these back-and-forth announcements every few months from each manufacturer as long-term follow-up data continues to trickle in. The question needing an answer is how long immune protection lasts following the initial HPV vaccination series. These results will help determine whether booster doses are needed, and if so, how often.

Among the advantages of these follow-up studies led by the vaccines' manufacturers is the head start it provides in advance of the vaccines' public debut. If immunity does wane at some point, we know (a) that it appears that it won't for at least 5 years and (b) there will be ample time to implement recommendations for booster doses well before the initial public vaccine recipients near the point at which immune protection would otherwise begin to fall.

Latest on Midwest mumps epidemic

We haven't written here yet about the mumps outbreak affecting Iowa and neighboring states in the Midwest, but stories in today's Washington Post and New York Times address the role of the mumps vaccine in the epidemic and also provide good overviews for those who haven't been following the story over the past several weeks. On the vaccine, from the Times...

"(CDC Director Dr. Julie) Gerberding said the disease had spread quickly because of the dense concentration of students in affected cities and because the vaccine is not perfect. It has about an 80 percent efficacy rate for people who have been inoculated with one dose, and a rate of about 90 percent for people who have received the recommended two doses.

'We have absolutely no information to suggest that there's a problem with the vaccine,' Dr. Gerberding said. 'What's going on here is basically a number of people who haven't received both doses, coupled together with people who have received the vaccine but are susceptible anyway, living in crowded conditions like college dormitories or mixing up with other students at spring break or during holidays, and setting up a cascade of transmission that's going to take a while to curtail.'"

The vaccine in question is Merck's M-M-R II, the only licensed mumps vaccine available in the United States. The stories report that CDC will be shipping 25,000 doses of the vaccine from its stockpile to affected areas and Merck will donate another 25,000.

For mumps, there are no specific risk behaviors that increase the likelihood of contracting it (other than not following standard hygiene recommendations -- although people should wash their hands, etc., for many more health reasons than the very slim chance of coming down with mumps). However, the quotes from the general public in both stories reflect near-amazement that it's even possible to get mumps in 2006. While a testament to the effectiveness of decades of vaccination, these views underscore the challenge of stressing the continued necessity of high vaccination rates and the importance of reminding the public that no vaccine guarantees 100% protection against an infection. This second point becomes particularly important when vaccines provide partial protection, as is the case with HPV (which targets viral strains accounting for only 70% of cervical cancers).