November 27, 2004
FDA Reviews When Bayer Revealed Drug Risks
WASHINGTON -- In a move that could lead to a criminal investigation, the government is checking its records to determine if drug maker Bayer AG was forthcoming about safety concerns with its cholesterol-lowering Baycol drug that surfaced within months of it hitting the market.
If this week's allegations prove true that the company knew but was slow to inform the government that its drug was riskier than comparable drugs, the Food and Drug Administration could begin a criminal investigation, one official said this week.Bayer internal company records now in the public domain indicated that by May 28, 1998, three months after the drug went on the market, people who took the drug with gemfibrozil, another cholesterol-lowering drug, had elevated levels of an enzyme that accompanies muscle injury or had developed a rare muscle-wasting disorder. Bayer did not warn doctors and patients not to take the two drugs together until December 1999, four scientists wrote in a Journal of the American Medical Association paper released this week.
In addition Bayer scientists knew in late 1999 and early 2000 that using Baycol alone "substantially increased the risk" of people getting a rare muscle-wasting condition, compared with a rival drug, but they did not immediately alert physicians or patients. FDA rules require speedy notification of serious side effects linked to drugs.
The JAMA article alleged that "before the agency was aware of the data, the company knew that the drug was more dangerous than others. If this allegation is correct, the FDA takes it extremely seriously and we're going to have our criminal investigators look into this," Dr. Steven Galson said during a C-SPAN appearance. Galson is acting director of the FDA's Center for Drug Evaluation and Research.
"Right now, we don't really know whether that's true or not," said Galson. "We read about it in this level of detail for the first time" in the JAMA papers, he said.
FDA spokeswoman Kathleen Quinn said, "Bottom line: We have to go back and look at all the data (to) see what we have and compare and make sure we had all we could have - which we think we did."
Bayer said in a statement that the JAMA articles "contain no new information regarding Baycol and Bayer's timely reporting of data. Bayer kept the FDA fully informed about all pertinent safety information, including adverse event reports. Indeed, an FDA audit of Bayer's postmarketing practices during the time Baycol was on the market demonstrated no deficiencies."
Its pharmaceutical division withdrew Baycol from the market on Aug. 8, 2001, after it was linked to a sometimes fatal muscle-wasting condition, rhabdomyolysis. By then, the FDA had received reports that 31 Americans died from severe rhabdomyolysis after using Baycol. Twelve of those people used Baycol in combination with gemfibrozil.
The company reported it paid $1.1 billion, without admitting liability, in out-of-court settlements of 2,895 cases related to Baycol side effects. The suits were filed after Baycol was withdrawn from the market. Some 7,169 cases are still pending.
Besides published scientific reports and FDA data, the authors of the JAMA paper reviewed internal Bayer documents that entered the public record due to lawsuits filed against the company.
In long-term clinical trials, cholesterol-busting statins atorvastatin, lovastatin, pravastatin and simvastatin were associated with lower risks of causing patients to develop the muscle-wasting condition, the JAMA paper said. Baycol represented only 2 percent of market share - 9.8 million of 484 million statin prescriptions written. Yet Baycol was linked to 57 percent of the muscle-wasting side effects reported by statin users between January 1990 and March 2002.
In an accompanying paper in JAMA, however, an attorney defended the company's actions and noted that at least two of the authors of the JAMA article had been paid experts in plaintiffs' lawsuits against Bayer.
"It always is possible to second guess decision-making after the fact," wrote Joseph D. Piorkowski Jr., outside counsel in Baycol litigation for Bayer Corp., the German drug maker's U.S. subsidiary. "However, when judged fairly by all the facts in their proper context, Bayer's conduct in the marketing of (Baycol) from 1997 to its voluntary withdrawal from the market in August 2001 was responsible, appropriate, and consistently motivated by concern about the safety and welfare of patients."
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