Tag Archives: GlaxoSmithKline

Can HPV Vaccination Be Simplified?

The human papillomavirus vaccine was recommended for routine use in 11-12 year old girls in 2007. But by 2010, the most recent year for which data are available, less than half had received one dose of the three-dose series and fewer than a third had received all three. The inconvenience of the need for three separate office visits along with the vaccine’s price – about $130 per Gardasil dose, as of July 2011 – have certainly contributed to the low uptake.

©BVDC/Fotolia.com

Now, some parts of the world – including Mexico, Switzerland, and parts of Canada have moved to either a two-dose schedule, or a so-called “extended dose” schedule, in which the third dose is delayed until 5 years after the second one. (In the current U.S. three-dose schedule, doses two and three are given at 2 and 6 months, respectively, after dose one.)

“There has been emerging interest in HPV vaccine schedules with fewer than three doses, for a variety of reasons. These schedules could facilitate implementation, they may be more convenient for providers, parents, and vaccinees, and of course they would be cost-saving,” said Dr. Lauri Markowitz, of the Centers for Disease Control and Prevention, at a recent meeting of the CDC’s Advisory Committee on Immunization Practices.

No data on the efficacy of fewer than three doses have been published by either Merck or GlaxoSmithKline from their pivotal trials of Gardasil and Cervarix, respectively. But some other data are available for both vaccines. A nonrandomized study in Costa Rica that included more than 1,100 women who had received just one or two doses of Cervarix suggested that two doses or maybe even just one – could be as protective as three doses against infection at 4 years.

And in an as-yet unpublished study done in Canada, immune responses against both HPV 16 and 18 at 3 years were similar between two doses of Gardasil given at age 9-13 years and three doses given at age 16-26 years. But, there are limited efficacy data and no long-term data, Dr. Markowitz said.

Electron micrograph of human papillomavirus (HPV) / Courtesy of the National Cancer Institute

In an e-mail, Deb Wambold of Merck Vaccines said that, while the company does support studies of alternative dosing schedules for HPV vaccination including two-dose regimens, so far those studies are “interesting preliminary explorations in select subpopulations of vaccinees,” and “It is important to note that there are no data on the clinical efficacy or durability of effectiveness with two doses of either of the HPV vaccines, as we have for the recommended three-dose vaccination regimen.”

Dr. Joseph A. Bocchini Jr., who chairs the ACIP HPV vaccine working group, concurred. In an interview at the ACIP meeting, he noted that the long-term efficacy of two doses is “worth looking at,” as is the varying of three-dose schedules. “But, at this point, there are too few data to apply this to recommendations in the United States.”

More data from ongoing trials will be available in the next few years, Dr. Markowitz said.

-Miriam E. Tucker (@MiriamETucker on Twitter)

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Filed under Allergy and Immunology, Epidemiology, Family Medicine, IMNG, Infectious Diseases, Internal Medicine, Obstetrics and Gynecology, Oncology, Pediatrics, Primary care, Uncategorized

The Truth About Avandia? You Can’t Handle the Truth

After sitting through about 17 hours of talk over the last two days about GlaxoSmithKline’s much-maligned diabetes drug Avandia (rosiglitazone), it’s still near impossible to tell exactly where the truth lies.

If you are to believe Glaxo, the truth does not lie.  Whereas David Graham, the FDA’s very own iconoclast, and Steven Nissen, the always-ready-with-a-quote Cleveland Clinic cardiologist, seemed to have had to sit on their hands to keep from bursting out, Joe Wilson-style, “you lie!”

Via Flickr Creative Commons user emdot

The July 13-14 joint meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee — a referendum on the drug’s safety — was a curious confluence of pro- and anti-Avandia forces, all of whom claimed to have science on their side (background materials posted here, on July 9).

I don’t usually like to bring myself into these posts, but I have been covering FDA advisory committee meetings for, oh, about 20 years, and I can probably count on one hand the number of times I’ve witnessed panel members, speakers, and FDA staff openly question the truthfulness of a manufacturer’s data submission.

No doubt that sloppy paperwork has always existed, but I don’t recall ever seeing it so vividly dissected and displayed in such a public forum.  Thomas Marciniak, an FDA medical reviewer who got handed the Avandia file last fall for the first time,  aired Glaxo’s dirty laundry multiple times over the course of the two days.  The self-acknowledged bloodhound of an investigator said that in Glaxo’s pivotal safety trial, RECORD, he found multiple instances of heart attacks disappearing off case reports and unreported deaths, even though the study ostensibly was focused on documenting cardiovascular events and mortality (his slides are here).

Even his boss, Ellis Unger (deputy director of the FDA’s Office of Drug Evaluation I), told the panel, “the issue here really is truth.” And Dr. Unger was avowedly in favor of keeping Avandia on the market.

The credibility conundrum seeped into panelists’ discussions.  Many expressed consternation over Dr. Marciniak’s findings, but in the end, 20 of the 33 panelists said that Avandia should remain available as an option for patients.

It’s uncertain when the FDA will make a decision based on these panelists’ advice — there is no statutory timeline for the re-review of an already-marketed drug.  But the Monday-morning quarterbacking has begun in earnest.

The New York Times played up the lack of credibility angle and portrayed Avandia as doomed. The Wall Street Journal said that analysts were factoring a big decline in sales into their overall estimates for Glaxo.

Meanwhile, the Union for Concerned Scientists called the meetings a “fiasco” in a press release. Public Citizen’s Health Research Group director Dr. Sidney Wolfe called on the FDA to immediately remove Avandia from the market. Mr. Wolfe spoke out against Avandia at the hearing (testimony here).

Meanwhile, the Endocrine Society, American Diabetes Association, and American Association of Clinical Endocrinologists put out a joint statement urging patients to talk with their physicians before giving up on Avandia.

So who to believe? Is Avandia safe? Is it dangerous?

The truth is, science is imperfect.

— Alicia Ault (on Twitter @aliciaault)

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Filed under Cardiovascular Medicine, Drug And Device Safety, Endocrinology, Diabetes, and Metabolism, Geriatric Medicine, IMNG, Internal Medicine