The blockbuster arthritis drug Vioxx was taken off the market yesterday by Merck & Co. after a study confirmed simmering concerns that it significantly raised the risk of heart attack and stroke. More than 2 million people take Vioxx worldwide, making this the largest voluntary drug recall in history.
Merck said it received new information last week showing that people who used the drug for more than 18 months had nearly twice as many serious cardiovascular problems as those on a placebo. By Tuesday, the company had told the Food and Drug Administration it planned to withdraw the drug.
“We believe it would have been possible to continue to market Vioxx with labeling that would incorporate these new data,” said Merck President Raymond Gilmartin. “However, given the availability of alternative therapies and the questions raised by the data, we concluded that a voluntary withdrawal is the responsible course to take.”
FDA officials said they would begin additional study of three other painkillers in the class called Cox-2 inhibitors, which were hailed as near-miracle drugs when they came on the market in the late 1990s. The officials said the other Cox-2 drugs have not been associated with the same dangers of stroke and heart attack but acknowledged that no patients using them have been followed for 18 months, as was the case with Vioxx.
The drug bought in $2.5 billion in worldwide sales last year and its withdrawal slashed the company’s stock price by more than $12 a share, reducing the company’s market valuation by more than a quarter.
Although Vioxx was aggressively marketed after it won FDA approval in 1999 and has been used widely, with more than 84 million prescriptions written, serious health concerns were reported soon after it became available. The FDA required additional warnings to the drug’s label in 2002, and several months ago it received the abstract of another report describing heightened cardiac and stroke risks with Vioxx. FDA officials said they were studying those results when Merck contacted them earlier this week.
Patients who claim to have been harmed by Vioxx had filed more than 200 lawsuits before yesterday’s announcement. Many of the cases have been consolidated into two major lawsuits in Los Angeles and New Jersey.
Merck officials stressed that there were no more than the expected number of deaths among the patients taking Vioxx in the new study and that they knew of no deaths that should be attributed to the drug. But the company, long one of the industry’s biggest and most respected, was clearly concerned about a potential onslaught of lawsuits.
Vioxx is the first prescription drug to be withdrawn since 2001, when the cholesterol-lowering drug Baycol was taken off the market.
In the four years preceding that, 11 drugs were withdrawn for safety reasons.
Yesterday’s announcement rekindled the debate over whether the FDA has been sufficiently aggressive in monitoring drug safety. The clinical trial that found the increased danger of cardiovascular disease in patients taking the painkiller was not designed to assess the drug’s safety, but to determine whether Vioxx protects against the recurrence of potentially cancerous intestinal polyps.
An independent panel monitoring the study advised the company Sept. 23 to stop the trial because the drug appeared to be increasing the risk for heart attacks and strokes. Patients taking the drug for more than 18 months appeared to face about double the risk for a major cardiovascular event, primarily heart attacks and strokes, compared to those taking a dummy pill.
The acting director of the FDA’s Center for Drug Evaluation and Research, Steven Galson, said the agency had been “closely monitoring” reports of serious side effects from Vioxx through its national adverse event reporting system. But he also said that because so many Americans suffer heart attacks and strokes, it’s been difficult to pin down how Vioxx might be related to the incidents being reported.
Because the FDA and Merck had been aware for some time of the reports of heightened health risks with Vioxx, the agency came in for harsh criticism Thursday.
Eric Topol, head of cardiology and chief academic officer of the Cleveland Clinic, called it “the right decision about three years too late. This is the sort of thing that Merck should have studied earlier, but they were too busy refuting the warning signs.” Topol was a co-author of the study that first suggested possible hazard from rofecoxib, the generic name of Vioxx.
While Topol said he isn’t sure his earlier analysis was enough to warrant yanking Vioxx in 2001, “it was enough to address this and get the right answer. We shouldn’t have to wait to get it from a study of patients with colon polyps.”
That view was shared by Jerry Avorn, a physician at Harvard Medical School who is an expert on the use and marketing of prescription drugs.
“When this question came up initially, the standard response from the FDA was to hope the company would do its own study to resolve it,” he said. “The FDA has not been brave enough in demanding that companies perform safety studies of this kind.”