Tuesday, September 8, 2009

Gardasil for Men and Boys: What the FDA Committee Will Discuss on September 9

A lot of people who read this site have already sent in comments about Gardasil for review by the VRBPAC (the FDA’s Vaccine and Related Biological Products Advisory Committee). Committee members will consider these when they meet on Wednesday to discuss approval of Gardasil for men and boys, along with approval of Cervarix, GlaxoSmithKline’s competing HPV vaccine, and a few readers have even applied to make an oral presentation during the brief public comment periods.

But what else will the committee be looking at?

Gardasil for preventing genital warts, not cancer, in men

Turns out that the focus will be on Gardasil for preventing genital warts, not cancer, in men. That’s because Gardasil is indeed pretty effective (67 to 89.4 percent) for preventing HPV-caused genital warts, which are estimated to affect roughly one percent of the population.

However, penile and anal cancers, which can also be caused by HPV, are very rare. Because the progression of lesions to cancer is not as clearly defined in penile/anal/perineal cancers as it is in cervical cancer, and because a “substantial percentage of penile cancers are known to arise in the absence of detectable HPV,” Merck agreed to change its original request. Instead of asking to have Gardasil approved for preventing “external genital lesions,” it asked to have Gardasil considered solely as a genital wart preventative. Although Merck did study a subset of, as they put it, MSMs (Men having Sex with Men) in an attempt to assess Gardasil’s effect on anal cancer rates, they chose not to submit the data at this point.

Merck has been heavily criticized, most recently in JAMA, for over-selling Gardasil as a cervical cancer preventative. As Drs. Sheila and David Rothman wrote in JAMA, “No data were available to establish the duration of efficacy, possible adverse effects on natural immunity, whether vaccinated women will forgo Papanicolaou tests, and whether after suppressing HPV-16 and HPV-18, other strains may emerge as significant oncogenic serotypes.” Merck is apparently not going to try to pull that one off this time around, or at least,not yet.

Merck submitted data on a randomized, placebo-controlled study of 4065 males aged 16-26.

The data showed the expected efficacy for genital wart prevention and a number of other things, too, one of which was that in the placebo group rates of infection rose substantially in non-circumcised men and in those who had multiple partners (something to think about, guys).

And “a marked reduction in efficacy was seen in the setting of pre-existing infection.” In other words, you may not want to bother getting it if you’ve already become sexually active—or else you may want to get an HPV test before shelling out about $360 plus the cost of administration.

Adverse Events

As to adverse events (AEs), the background information that the VRBAC will consider didn’t show anything insanely significant. 69.2 percent of the Gardasil group versus 64.2 percent of the aluminum placebo group reported AEs, with notably more reporting injection site issues. Injection site AEs were far less frequent in the very small saline placebo group than in the much larger aluminum placebo group. 24.2 percent (Gardasil) versus 22.8 percent (placebo) reported new medical conditions.

Merck has been widely criticized for using an aluminum adjuvant in the placebo group, as such a practice can mask adverse reactions. Aluminum is somewhat suspect as a potential trigger for autoimmune and neurological disorders.

As with female populations, Gardasil appears to pose a somewhat higher risk of arthritis. 30, or 1 percent, of the Gardasil group developed arthralgia, arthritis, or reactive arthritis as opposed to 17, or 0.7 percent of the placebo group. There were also 3 (0.1 percent) versus 0 cases of hypothyroidism.

However, when all was said and done, the same percentage—1.4 percent—of both groups developed autoimmune disorders in the short term. There were no reports of the autoimmune diseases that have anecdotally been reported as occurring post-Gardasil in women and girls, such as the ALS-like “neurological disease mediated by immune responses” that, according to the autopsy, led to extensive damage in Jenny Tetlock’s spinal cord, and eventually to her death at 15. Gardasil has also been associated with Graves Disease, epilepsy, lupus, and various other immune disorders as well as multiple deaths. The FDA has not found that these conditions occurred significantly more frequently than in the overall population, although it recently warned that it was certainly associated with a higher number of blood clots as well as syncope.

The placebo group consisted of 2033 males injected with the aluminum adjuvant and just 322 injected with saline. Perhaps one day the FDA will demand a real placebo-controlled study of the adverse effects of vaccination, using saline only as a placebo.

A lot of the discussion about Gardasil for men and boys has focused on giving it to young boys as a way of preventing HPV in their future partners. That’s an unusual departure for a vaccination, although it still contributes to one of the goals of vaccination—“herd immunity.” The VRBPAC, however, will not consider this issue. Nor will it consider the potential for educating people about how not smoking, getting circumcised, eating lots of fruits and vegetables, delaying sexual activity, using condoms (about 70 percent effective) and limiting sexual partners, can all help people to dramatically reduce rates of persistent HPV infections. That might be a reasonable alternative for many people, rather than burdening growing bodies with yet another vaccine.

Instead, the VRBPAC will look solely at whether “the overall risk/benefit ratio” is favorable for approval of Gardasil as a means of preventing genital warts in men, and whether the post-marketing plan is adequate for assessing safety. That’s it.

My guess is that Gardasil will be approved for men and boys, and will join the ever-increasing number of vaccinations recommended for all children. Every parent and every young adult will have to sort through the pros and cons for themselves. Don't forget to honestly considering your lifestyle and your family history of autoimmune disease while making that decision.


Brian said...

I am a man 20 years old and I got the Gardasil vaccine and I have not had any problems. The only thing that I see that is bad is about 20 minutes there is a lot of pain and a scale 1 to 10 it was a 10. But, what is a little pain compared to the viruses?

Brian said...
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Kristin Johns said...

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