WASHINGTON (Reuters) - Safety questions around a GlaxoSmithKline PLC GSK.LGSK.N diabetes pill pose a major test for the U.S. Food and Drug Administration's leadership and how it will handle drug risks under President Barack Obama.
The fate of Glaxo’s Avandia is the first big side-effect controversy since FDA Commissioner Dr. Margaret Hamburg and Deputy Commissioner Dr. Joshua Sharfstein, chosen by Obama, took over the agency more than a year ago.
Both are public health advocates who have championed science in the interest of patients.
Now doctors, patient advocates, drugmakers and investors are watching to see how the new FDA leaders will rule on safety concerns raised by data that paints a mixed picture of Avandia. An FDA advisory panel is due to weigh in next month.
Consumer groups, an outspoken cardiologist, at least one lawmaker and some FDA staff are pushing to get Avandia off the market. But the drug has had high-level backers at the agency since scrutiny of heart attack risks began three years ago.
“It’s clearly a challenge for Margaret Hamburg,” said Ira Loss, an analyst with Washington Analysis.
Consumer advocates criticized the FDA under President George W. Bush as being too close to drugmakers and unwilling to take strong and quick steps against medicines that drew safety complaints after they hit the market.
The Avandia case presents “a real test for the FDA to show, hopefully, that times have changed,” said Diana Zuckerman, head of the National Research Centre for Women & Families.
Inside the FDA, opinions are mixed. Staff in the office that tracks side effects after a drug’s approval have argued since 2007 that Avandia increases the chances of a heart attack and offers no unique benefits to justify future sales.
Senior FDA drug officials have backed Avandia, saying diabetics risk major complications such as heart disease, blindness and amputations from their disease, and need multiple treatment options.
The pill now comes with an agency-approved warning that it may raise heart-attack risk but it says the data is “inconclusive.”
One FDA reviewer, whistleblower David Graham, released a study this week concluding Avandia was more dangerous than a rival medication, Takeda Pharmaceutical Co's 4502.T Actos, for U.S. Medicare patients.
Cleveland Clinic cardiologist Steven Nissen, another vocal Avandia opponent, also updated his 2007 study that set off the furore over the drug. His review said the drug increased heart attack risk at least 28 percent.
In Congress, Democratic Representative Rosa DeLauro said those studies “make it even more difficult for the FDA to justify keeping this dangerous drug on the market.” DeLauro controls a subcommittee that sets the FDA’s annual funding. Republican Senator Charles Grassley also has sharply criticized the agency’s oversight of Avandia.
Maker Glaxo has vigorously defended the drug. The company said six randomized clinical trials, the gold standard for medical studies, showed Avandia did not increase the overall risk of heart attack, stroke or death.
While opponents have been more vocal than Avandia’s backers, many doctors still support the medicine, as seen by global sales of more than $1.2 billion (796 million pounds) a year.
That is down from a peak of $3-billion-a-year and the medicine is now a relatively small product for British drug giant Glaxo. The company could, however, face more lawsuits if Avandia is pulled off the market.
A showdown will come when an FDA panel of outside experts meets July 13 and 14 to sort through piles of conflicting data and hear from major critics and boosters of the drug.
The panel could recommend keeping the drug on the market, possibly with advice to limit it to certain patients, or could suggest the drug come off the market.
NOT A DONE DEAL
Despite the public pressure, “it is far from a done deal that the committee will recommend that this product be taken off the market,” said Loss, the analyst. A 2007 advisory panel voted 22-1 that Avandia could still be sold.
Loss and other analysts say a key to the outcome is who the FDA appoints to the panel. Cardiologists may be more likely to oppose the drug while diabetes-treating endocrinologists could be inclined to support it.
The FDA usually follows the recommendations of its panels, but is not required to take their advice.
The final decision may have wider implications. The ruling will give a sense of the agency's thinking about drug safety in general since the recall of Merck & Co's MRK.N painkiller Vioxx in 2004 over a link to heart attacks and strokes.
Consumer advocates used the Vioxx case to urge caution and stricter oversight, while companies balked at what they saw as a shift to a more conservative stance that stifled their ability to bring products to market.
If FDA decides Avandia should no longer be sold, it could signal a tougher hurdle for future medicines with marginal safety problems, Morningstar analyst Damien Conover said.
“The ability to get through FDA might be questioned a little bit more if they were to do something pretty dramatic here,” he said. Conover thinks a ban is unlikely.
The FDA is promising to review all scientific evidence on Avandia to make a decision. After that, the challenge will be convincing the public it made the best choice.
“It’s important whatever we decide that we explain it very well,” FDA’s Sharfstein said.
Reporting by Lisa Richwine and Susan Heavey; additional reporting by Julie Steenhuysen in Chicago; Editing by Tim Dobbyn
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