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Celebrex Should Stay on Market, Despite Heart Risks: FDA Panel

Posted on: Friday, 18 February 2005, 15:02 CST

FRIDAY, Feb. 18 (HealthDay News) -- The popular painkiller Celebrex significantly raises cardiovascular risks but should be allowed to stay on the market, a U.S. Food and Drug Administration panel recommended Friday.

The advisory group, ending three days of hearings, approved continued use of the prescription arthritis drug by a vote of 31-1 after unanimously finding that the drug carries increased heart risks.

Next, the panel, a joint meeting of the FDA arthritis and drug safety committees, was to consider patient populations in which the benefits would outweigh the risks, and was also weighing the question of a black-box warning for the entire class of painkillers known as cox-2 inhibitors.

The fate of two other cox-2s, Bextra and the now-withdrawn Vioxx, was to be determined later Friday.

The rapid Celebrex vote followed a summation by committee chairman Dr. Alastair Wood, who made it clear Friday morning at the end of public testimony that there were significant safety issues posed by the cox-2s.

"It's important to recognize that this is a far larger randomized safety signal than we have seen from any of the drugs that have been withdrawn for safety reasons," Wood told the assembled crowd.

"This is a much bigger safety problem than with the other drugs the FDA has withdrawn," Wood added. "And the only reason we have agonized so much is that this is a relatively common problem, and therefore much harder for us to be sure the signal is clear."

While acknowledging that patient testimony heard on Thursday was "both moving and important," Wood, of Vanderbilt University Medical School, added, "No one has been able to demonstrate specifically a better response amongst any of these drugs in individual patients in any randomized way."

All of this, he added, brings the panel of 32 scientists and doctors to the $64 million question: "What should we do?"

"The committee needs to act in a way that limits the hazard to patients," he said. "The public has a right to expect us to do that. When we leave here tonight, we need to have made really clear recommendations to the FDA, which will help them move forward."

Wood's remarks came right after representatives of drug companies made last-ditch presentations in defense of their products.

And they followed Thursday's surprise announcement that the manufacturer of Vioxx may put the painkiller back on the market if the advisers recommend the benefits of cox-2 drugs outweigh increased heart risks that have shown up in numerous studies.

"If the advisory committee and the FDA conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers," the Merck & Co statement said, according to a CNN report.

Vioxx was pulled off pharmacy shelves by Merck last fall after company trials showed an increased risk of heart and stroke damage.

In its statement, according to CNN, Merck said it had learned new clinical data about other drugs during the FDA hearings.

"Since we withdrew Vioxx from the market, the science has continued to evolve and new data on some of these alternative therapies have become available," the company statement said.

The popularity of painkillers like Vioxx was very much in evidence during testimony from the public at the hearing. At least a dozen people took to the podium with personal stories of pain relief and asked the FDA advisers to keep the cox-2 inhibitors on the market.

Meanwhile, the European Medicines Agency, Europe's most powerful drug regulators, on Thursday trumped the FDA and mandated stronger warnings on cardiovascular risks for all the cox-2 painkillers, the Associated Press reported.

Early Thursday, FDA whistleblower Dr. David Graham delivered damning testimony on Vioxx and the other cox-2 inhibitors, the class of painkillers originally designed to reduce the risk of gastrointestinal danger .

"There's a one-in-50 chance that a male aged 65 to 74 will have a heart attack this year. Increase that fivefold with high doses [of Vioxx]," Graham told the FDA advisers.

"That's what happened with VIGOR [a 2000 manufacturer's trial comparing gastrointestinal effects of Vioxx and another painkiller, naproxen]. If you have millions of people taking high doses, you're going to get numbers that balloon out. Because of the high background rate of the underlying event, there are many more cases," he said.

The fact that randomized controlled trials such as VIGOR tend to include healthy people may have skewed the perception of risk, the FDA scientist added during two hours of testimony.

"People are harmed by rofecoxib [Vioxx]," Graham testified before a standing-room-only crowd.

The U.S. hearings resulted, in part, from Graham's outspoken criticism of Vioxx. The medical officer for the FDA's Center for Drug Evaluation and Research has charged he was censured for trying to reveal information about the drug.

At Thursday's hearing, he thanked acting FDA Commissioner Dr. Lester Crawford, who he said "exercised great leadership" in allowing him to present the information he wanted to present.

In their testimony, both Graham and Dr. Richard Platt, of Harvard Medical School, tried to demystify the different types of studies available on nonsteroidal anti-inflammatory drugs (NSAIDs), the group of medications that includes cox-2s.

While Platt was matter-of-fact in his descriptions of how different studies are designed and how that might affect outcomes, Graham was more forthcoming on which specific studies he deemed good or bad.

Graham said he believed the negative cardiovascular effects of Vioxx were dose-dependent, meaning higher doses had a bigger effect, and that the risk kicked in immediately, within the first 30 days. Both issues have been subjects of debate.

Celebrex had no effect on the heart at doses of 200 milligrams or less, Graham added, but did have an increased risk at higher doses. Naproxen, which is a traditional NSAID, has no protective effect, he contended.

And, he added, the little information that exists on Bextra indicates no risk at small doses.

More information

More about the hearings is available at the FDA.

SOURCES: Feb. 17, 2005, U.S. Food and Drug Administration (FDA) advisory panel hearings, with Richard Platt, M.D., Harvard Medical School, and David Graham, M.D., medical officer, Center for Drug Evaluation and Research, FDA, Washington, D.C.; CNN; Associated Press~SAFP~~ARTD~~HATT~~PRES~~STRO~~FDA-~

Source: HealthSCOUT

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