Merck May Resume Sales of Painkiller, Official Says

By GARDINER HARRIS

Published: February 18, 2005

WASHINGTON, Feb. 17 - A top Merck research official suggested to a federal drug advisory panel on Thursday that the company might soon decide to start reselling the painkiller Vioxx in the United States, despite risks it may pose to the heart.

The official, Dr. Peter Kim, Merck's research chief, said that if the panel decided that Celebrex and Bextra, drugs similar to Vioxx, also hurt the heart, "then that would be important to us to take that into consideration with regard to Vioxx."

Dr. Alastair Wood, the chairman of the advisory panel reviewing drugs in a class known as cox-2, asked Dr. Kim what he meant. "Are you saying that if we think that the cardiovascular risk is a class effect, then you would consider putting Vioxx back on the market?" Dr. Wood asked.

Dr. Kim did not answer directly, but said: "The science has progressed. There are unique benefits to Vioxx."

In a statement, Merck said, "If the advisory committee and the F.D.A. 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."

In their comments in the last two days of a three-day hearing, panel members have said they believe that all the cox-2 drugs - which include Vioxx, Celebrex and Bextra - carry heart risks. But the panel now must compare the drugs' benefits with their risk.

Dr. Paul Seligman, a top F.D.A. official, said it was too early to determine how the agency would respond if Merck sought to resume Vioxx sales.

The news was a remarkable disclosure in an already landmark hearing. Panel members have been sifting through studies trying to weigh the risks and benefits of Vioxx, Celebrex and Bextra. None of the drugs cure pain any better than older medicines. They were developed with the hope that they would cause fewer ulcers than older medicines, but Merck withdrew Vioxx in September after a study showed that the drug doubled the risks of heart attack and stroke.

Since then, more studies have shown similar risks for Celebrex and Bextra. The agency called the committee together to tell it what to do. According to much of the testimony, the committee will probably suggest that the drugs stay on the market, with tough warnings about risks.

"I don't think any one of us is saying that these drugs should be taken off the market but that they should be used at the lowest safest dose," said Dr. Gary Hoffman of the Cleveland Clinic.

Dr. Michael Domanski of the National Institutes of Health agreed, saying, "It's pretty clear that there is an excess risk confirmed by some or all of these drugs."

The problem, many committee members said, is that patients who are at high risk of developing ulcers are often the same ones who are at risk of heart attacks.

"Finding the sweet spot for these drugs becomes a little bit harder," said Dr. Steven Nissen, a panel member from the Cleveland Clinic. "Older people are at greater risk for gastrointestinal bleeding, and I can assure you that they are greater risk for coronary disease."

Trying to find the right balance between the risks and benefits will be the committee's task on Friday. Dr. Wood said that had the advisory panel known about the cardiac risks years ago, it would probably not have voted to approve the drug. But he said something had to be done.

"The number of events that these drugs are going to cause are going to be vastly in excess of anything we've seen before," he said, "so we have to do something."

Several panel members also expressed frustration that the F.D.A. did not have the legal authority to force drug makers to test approved medicines when concerns were presented about their safety.

"I would like to see Congress empower F.D.A. to mandate these kind of trials as these situations occur," said Dr. John Cush, a rheumatologist from Dallas.

Among the most widely anticipated presentations was that of Dr. David Graham, a drug-safety officer for the agency who has sometimes feuded with top agency officials. Dr. Graham suggested that taking high doses of cox-2 drugs hurt the heart even more than smoking, diabetes or high blood pressure.

He said the cox-2 drugs did not seem to have clear benefits to outweigh those risks. The drugs are supposed to cause fewer ulcers than older pain pills, although evidence for that effect has been mixed. Dr. Graham said that 40 percent of those who suffered heart attacks died, compared with 5 percent who suffered serious ulcers. But Dr. Graham also condemned Indocin and Mobic, both popular painkillers.

A study of California Medicaid patients found that Indocin, known generically as endomethacin, nearly doubled the risks of heart attacks in patients, Dr. Graham said.

For Mobic, the risks of heart attack and stroke rose 37 percent, Dr. Graham's study showed. Mobic is manufactured by Boehringer Ingelheim. In the wake of Vioxx's withdrawal and news that Celebrex and Bextra may hurt the heart, sales of Mobic have risen sharply. Dr. Graham suggested that the move toward Mobic was a problem. Several panel members expressed skepticism because the findings were derived from observational studies, which are not completely trustworthy.

Dr. Christopher Grubb, a captain in the Army Medical Corps, said soldiers in the 82nd Airborne were required to carry a cox-2 drug in the event of a battlefield injury. Dr . Grubb said the drugs had allowed many soldiers who otherwise would have been sidelined by pain to be deployed overseas.

The drugs, he said, "are essential for our global war on terrorism." The comment prompted loud laughter in the meeting.