A consumer advocacy group, Public Citizen, has petitioned the FDA to pull the drug, Uloric, off the market.
In November 2017, the U.S. Food and Drug Administration (FDA) alerted the public about preliminary results from a safety clinical trial of Takeda Pharmaceuticals’ Uloric (febuxostat) to treat gout. The drug was originally approved in 2009, but the agency required the company to conduct the safety study, and the drug already carried a Warning and Precaution label about possible cardiovascular events. At that time the agency said it intended a full review of the safety study.
In March, a full review was released. Yesterday, a consumer advocacy group, Public Citizen, petitioned the FDA to pull the drug off the market, stating, there is “overwhelming evidence that the serious cardiovascular harms of [Uloric] outweigh any purported clinical benefit.”
Gout is a metabolic disease, a type of arthritis, caused by uric acid crystal accumulation in the joints, the kidneys, and other tissue. It can lead to kidney damage, such as uric acid nephrolithiasis and interstitial kidney disease. Its first manifestation is typically the big toe, as well as the foot joints, ankles, and knees.
Traditional treatment is anti-inflammatory drugs like colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. Dietary treatments include limited intake of purines, alcohol, and fructose-containing foods, avoiding diuretics, and increasing fluid intake.
The FDA rejected Uloric in 2005 and 2006, when it was being submitted by TAP Pharmaceutical, on the basis of cardiovascular risk concerns. During the second submission, the FDA pointed out that nine of the total 12 deaths among patients receiving Uloric, cardiovascular problems were the cause, while there were no serious adverse cardiovascular events in the allopurinol or placebo groups.
According to IMH Health, from June 30, 2014 through June 30, 2015, Uloric was the 46th most-prescribed brand-name drug in the U.S., with 1.3 million prescriptions. The company reported $1.9 billion in U.S. sales from 2012 through 2017.
Earlier clinical trials had incidences of deaths related to respiratory failure, congestive heart failure, and coronary artery disease, although these are common in the patient population, and investigators concluded they were not related to the medication.
In March 2018, The New England Journal of Medicine published the results of the safety study, which concluded, “In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol.”
Takeda shortly afterward stated that it had not identified the reason for the imbalance in cardiovascular deaths.
“The agency should have demanded that an appropriately designed clinical trial to assess febuxostat’s cardiovascular risks be conducted before, not after approval,” said Michael Carome, director of Public Citizen’s Health Research Group, in a statement. “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.”
Public Citizen also argues that Takeda has not provided enough data proving the drug is more effective in preventing gout flares other than its ability to lower serum uric acid levels, which can cause acute gout episodes.
The FDA at this time indicates it will review the Public Citizen petition and respond directly to the organization.
