WASHINGTON — Federal regulators and the drug maker Merck & Co. were aware of risks that the company's Vioxx painkiller could cause serious heart problems before the drug was approved in 1999, government and expert witnesses told a Senate committee Thursday.
One government official warned that the Vioxx debacle was only one sign that the nation's drug-oversight system had left Americans "virtually defenseless" against dangerous pharmaceuticals. Vioxx was removed from the market Sept. 30, but the official asserted that five other widely used drugs deserved a critical reevaluation of their risks.
Dr. David J. Graham, a scientist with the Food and Drug Administration office that monitors drugs already on the market, cited the cholesterol-lowering drug Crestor; the weight-loss medication Meridia; Accutane, which is prescribed for acne; Bextra, a pain reliever; and Serevent, an asthma drug.
Manufacturers and Graham's superior at the FDA disputed the assertion that there were serious problems with those drugs.
Graham, a 20-year FDA veteran who is the associate director for science at its Office of Drug Safety, testified before the Senate Finance Committee that severe problems existed in the drug regulatory system. He called the Vioxx episode "a profound regulatory failure" that had probably cost thousands of lives.
"I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx," he said.
Based on risk levels suggested by Merck's own studies and clinical trials, Graham estimated that as many as 139,000 Americans who took Vioxx for arthritis, back pain and other ailments may have suffered serious side-effects. "Of these, 30% to 40% probably died," Graham told the Senate panel. "For the survivors, their lives were changed forever."
Graham's estimates, which were disputed by his FDA superior at the hearing, suggested that 26,000 to 55,600 patients might have died as a result of taking Vioxx.
Merck pulled Vioxx from the market after the company's data showed that the drug nearly doubled the risk of heart attacks and strokes among people taking it for at least 18 months.
About 20 million Americans have taken the drug.
Merck and the FDA strongly disputed the allegations that they ignored potential dangers of Vioxx, saying that solid evidence linking the medication to heart attacks was not developed until days before the drug was pulled from the market.
"Merck believed wholeheartedly in Vioxx," company Chairman Raymond V. Gilmartin, told the committee. "I believed wholeheartedly in Vioxx. In fact, my wife was taking Vioxx until the day we withdrew it from the marketplace." Earlier concerns about the drug were not grounded in hard data, he said.
Manufacturers and Graham's FDA superiors discounted the scientist's contention that problem drugs remained on the market.
"I do not have reason to believe that set of five drugs is specifically more concerning than other drugs we are looking at," said Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs.
Kweder also took issue with Graham's estimate of the potential harm caused by Vioxx. Noting that his numbers were based on a statistical calculation, she said, "These are not real deaths." And she defended Merck: "I believe Merck acted responsibly once the problem was recognized."
But committee Chairman Charles E. Grassley (R-Iowa) said he was concerned that the FDA "has a relationship with drug companies that is too cozy."
Grassley said he was considering reforms that would make the drug safety office in which Graham worked independent of the FDA unit that approved new drugs. The safety office currently reports to the unit that evaluates and approves new drugs.
"It doesn't make any sense from an accountability standpoint to have the office that reviews the safety of drugs that are already on the market to be under the thumb of the office that put the drugs on the market in the first place," Grassley said.
Graham testified that prior to the approval of Vioxx, a Merck study found a nearly sevenfold increase in heart attack risk with a low dose of the medication. But "the labeling at approval said nothing about heart attack risks," he said.
Two medical school professors -- Gurkirpal Singh of Stanford University and Bruce M. Psaty of the University of Washington in Seattle -- reviewed company and FDA documents for the committee and generally concurred with Graham's criticisms.
The company documents are proprietary, and most were not released to the public.
But a Merck memo released Thursday evening by the committee showed that company scientists hypothesized as early as November 1996 that patients taking Vioxx would have higher rates of heart problems than those taking an aspirin treatment in a comparison trial.
