February 18, 2005

Vioxx Alternative Potentially as Risky, Official Says


By Marc Kaufman

David J. Graham, a veteran Food and Drug Administration safety officer and recent whistle-blower, told a conference reviewing the risks of arthritis painkillers yesterday that Mobic, the medication that hundreds of thousands turned to after Vioxx and other COX-2 inhibitors came under a cloud, is potentially just as dangerous.

Graham said a large new study he and a colleague had just completed, which FDA officials initially did not want him to present because it was preliminary, indicates that the anti-inflammatory drug is a "bad actor." His agency, he added, needs to "weed the garden of bad actors."

Mobic is now the top-selling prescription arthritis painkiller, and its manufacturer strongly defended its safety record yesterday.

Graham, who was the star witness at an earlier Senate hearing into the withdrawal of Vioxx and the FDA's monitoring of drug safety, again delivered dramatic and controversial testimony yesterday.

In addition to strongly questioning the safety of Mobic, Graham said the cardiovascular risks of taking higher doses of COX-2 inhibitors are comparable to the dangers posed by smoking, high blood pressure and diabetes. He said he does not see any good reason for consumers to use drugs in that class now that the evidence is becoming more convincing that they all increase the risk of heart attacks and strokes, and may not provide better pain relief than older analgesics such as ibuprofen, naproxen or aspirin.

Graham's conclusions about COX-2 drugs were supported by many other speakers at the FDA-convened conference, including some who are studying COX-2 drugs that are still under development.

At the end of the unusual three-day session today, the panel of experts is scheduled to recommend to the FDA whether it should issue warnings about COX-2 drugs or restrict their use.

The difficult decisions facing the panel became increasingly clear with Graham's critique of Mobic and impassioned pleas from arthritis sufferers not to deprive them of drugs that relieve their pain. Many said the experts are focusing too narrowly on drug risks and minimizing their benefits.

Sales of Mobic, or meloxicam, have grown significantly since Merck & Co. stopped selling Vioxx in September and Pfizer Inc. decided in December to stop advertising Celebrex because of concerns about possible safety risks. Mobic, which had 3 percent of the market for arthritis drugs in September, now accounts for more than 9 percent.

John Yonsky, a spokesman for the German firm Boehringer Ingelheim GmbH, which makes the drug and distributes it with Abbott Laboratories, said Graham's comments "were a surprise to us and to many people." He said that neither the company nor the FDA has seen any serious cardiovascular side effects from Mobic since it was approved in 2000.

"This was preliminary and unpublished data that was presented, and we have no way to address it," Yonsky said. "All I can say is that more than 10 million people have taken Mobic in 100 countries, and we've seen no trends towards excess risk of cardiovascular events."

Graham almost did not present his new data about Mobic and other nonsteroidal anti-inflammatory drugs yesterday because of opposition from his FDA supervisors. Because of last-minute changes, copies of his presentation were not available to the large crowd at the Gaithersburg meeting until after the session began.

A drug safety officer for 20 years, Graham has emerged as a powerful voice for change at the FDA. Lionized by some and attacked by others, he has become undeniably influential. In the past 10 years, he has identified 11 drugs as unsafe, and nine were ultimately removed from the market.

At the beginning of his talk, Graham thanked Lester Crawford, recently nominated to be permanent commissioner of the agency, for allowing him to present the new data, which were drawn from an ongoing study of prescribing and disease databases collected by the California Medicaid program. It is unusual for such research to be presented publicly before it has been peer-reviewed and published, but Graham pushed hard to do so. In recognition of the unusual circumstance, he said that he was presenting his views on Mobic, and some other drugs, as an individual, not as an FDA official.

Some panel members and speakers said they objected to the presentation. John H. Klippel, president of the Arthritis Foundation, said the information about Mobic could cause panic and despair among arthritis sufferers.

"I don't think showing slides of data and hearing a person present their opinion is equivalent to a scientific vetting of a study," Klippel said. "The public and interested parties have to scrutinize this data before people start acting on it."

Klippel echoed the complaint of some arthritis patients who testified. "We've lost touch with the benefits of these drugs, which are considerable," he said.

An Army physician testified yesterday that COX-2 drugs "are essential to the global war on terrorism" and should be kept on the market despite their risks. Christopher Grubb said that without the drugs, the military cannot keep as many soldiers functioning on the battlefield. He said the military is concerned about the bleeding that can come with drugs such as aspirin.

But other speakers argued for dramatic action by the FDA.

"Unfortunately, drugs that are studied on a few hundred or few thousand people for a few weeks or months are then taken by millions of people for many years," said Diana Zuckerman, president of the public-interest group National Research Center for Women & Families. "If you're not sure that a product is safe or likely to be used safely, get it off the market."

Also yesterday, Merck Research Labs President Peter Kim said his company will consider returning Vioxx to the market if the panel concludes that its risk-benefit ratio is similar to that of other COX-2 drugs.

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