June 21, 2018

FDA Should Pull Twice-Rejected Gout Medication Off the Market

Agency Has Overwhelming Evidence That Medication Increases Risk of Death

WASHINGTON, D.C. - The U.S. Food and Drug Administration (FDA) should immediately remove from the market the widely used gout medication febuxostat because it poses unique, serious risks – some fatal – for no unique benefit, Public Citizen said today in a citizen petition to the agency.

There is “overwhelming evidence that the serious cardiovascular harms of febuxostat outweigh any purported clinical benefit,” the petition states. Leaving it on the market ensures “further preventable harm” to patients. Febuxostat is sold by Takeda Pharmaceuticals America under the brand medication Uloric.

Initial clinical trials testing febuxostat prior to FDA approval linked the medication to possible increased risks of serious adverse cardiovascular outcomes, including heart attack and stroke, and death. The FDA rejected the medication twice over these safety concerns before approving it in 2009 on the condition that the manufacturer conduct a large, post-market randomized clinical trial to further evaluate the cardiovascular risks.

In the decade since, the medication “has been aggressively marketed and prescribed to at least hundreds of thousands of patients … who were unaware of the potential dangers,” Public Citizen’s petition states. Takeda reported $1.9 billion in U.S. sales of febuxostat from fiscal years 2012 through 2017. For the one-year period ending in June 2015, there were 1.3 million U.S. prescriptions for Uloric, making it the 46th most prescribed brand-name medication in the U.S at the time.

“Before the FDA approved febuxostat, there was troubling evidence strongly suggesting that the medication increased the risk of serious adverse cardiovascular events and death, and the agency should have demanded that an appropriately designed clinical trial to assess febuxostat’s cardiovascular risks be conducted before, not after approval,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “The results of the FDA-mandated post-market trial now provide additional high-quality evidence of a causal link between treatment with febuxostat and an increased risk of death, particularly death from cardiovascular causes.”

Results of the FDA-mandated post-market clinical trial finally were published in the New England Journal of Medicine on March 12, 2018. The study enrolled more than 6,000 gout patients who had a history of major cardiovascular disease. The subjects were randomly assigned to receive either febuxostat or the much older gout medication allopurinol. The trial demonstrated that after 32 months, subjects receiving febuxostat were significantly more likely to die from any cause and from cardiovascular causes.

Importantly, there also is no evidence from this post-market trial or any prior trials that febuxostat is more effective than allopurinol in preventing acute gout attacks or other clinically important complications of gout, the most crucial reasons for using such treatments. “The FDA almost certainly would have denied approval of febuxostat if data from this post-market trial had been available at the time of the initial submission. The only justifiable course of action to prevent further cardiovascular deaths is obvious: This medication must be removed from the U.S. market immediately,” Carome said.

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