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Two drug makers spar with FDA panel over safety of arthritis medicines

WASHINGTON—Two top drug makers defended their decisions Wednesday to market painkillers that have been linked to an increased risk of heart attack, but a panel of medical experts questioned whether the companies had dug deeply enough to expose potential hazards.

The comments came at a hearing of advisory committees of the federal Food and Drug Administration, called in response to evidence that a class of arthritis painkillers known as COX-2 inhibitors can trigger heart attacks and strokes in some patients.

Some researchers fear that many thousands may have died as a result.

One of those painkillers, Vioxx, was pulled from the market Sept. 30 after its manufacturer, Merck & Co. Inc., received data showing that the drug raised the risk of heart attacks and strokes. Pfizer is the manufacturer of the two other COX-2 drugs, Celebrex and Bextra, which remain on the market.

Several panel members said that a primary purpose of the three-day hearing, which could result in a recommendation to restrict marketing of COX-2s or to ban them, was to weigh the known benefits of the drugs against their potential hazards.

"We say over and over again that all drugs have risk," said Dr. Steven Galson, the acting director of the FDA's Center for Drug Evaluation and Research. "When an (adverse) event is discovered, the faulty assumption is sometimes made that the drug should never have been approved."

The stakes at the hearings are high, not only for Pfizer and Merck, which face an avalanche of lawsuits from patients, but also for FDA officials, who have been forced to defend their drug approval procedures amid a public uproar over the safety of COX-2s.

The stakes are high as well for public health officials faced with what appears to be a difficult choice between the benefits of the drugs, which include the potential to prevent some forms of cancer, and their potential for harm.

The hearing quickly evolved into a clash of competing studies showing different reactions to the drugs.

Dr. Garret FitzGerald of the University of Pennsylvania School of Medicine, who was the first to identify the potential cardiovascular risk of COX-2 inhibitors in 1998, said the cardiovascular risks of the drugs are well established, with five studies clearly demonstrating the problems.

FitzGerald said the drugs can suppress the body's production of prostaglandins, substances that protect against heart disease.

But he also argued that COX-2 inhibitors can be beneficial for patients by protecting against intestinal bleeding and noted later that they may prevent pre-cancerous lesions of the colon.

The key is to screen carefully patients who may be more vulnerable to heart disease before administering the drugs, he said.

Dr. Ernest Hawk of the National Cancer Institute said there is compelling evidence that COX-2 inhibitors and other painkillers reduce the risk of intestinal cancer.

"Based on this abundance of literature we believed ... these reactions reduce the risk of colon cancer, and moreover those benefits may extend to other organs as well," Hawk said.

Dr. Ned S. Braunstein, senior director of research laboratories at Merck, said conclusive evidence of the harmful side effects of Vioxx did not emerge until September, when the company promptly withdrew the drug.

Merck had agreed to place a label warning of the potential risk to heart patients on the drug in 2002, after some preliminary results suggested problems. But the FDA panel expressed some skepticism over why the label did not appear until 14 months after evidence emerged.

Braunstein's testimony also drew questions from panel members who wanted to know why Merck did not follow up with patients who had dropped out of its studies. Had the company done so, the rates of cardiovascular risk might have gone up, some panel members maintained.

Despite the skepticism, Dr. Kenneth Verburg, a Pfizer scientist, suggested that his company's drug, Celebrex, had demonstrated benefits and said the issue of whether there are cardiovascular risks deserves further study.

"It's important to remember why we are at this hearing. This is a drug ... for which the reason to give the drug is to reverse adverse events," said Dr. Alastair Wood, who headed the hearing. "It is certainly worrisome when a drug is supposed to be providing safety benefits seems to be causing mortality."


(c) 2005, Knight Ridder/Tribune Information Services.

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