FDA Panel Opens Door For Return Of Vioxx
The Washington Post
By Marc Kaufman
Published February 19, 2005
A Food and Drug Administration expert advisory panel narrowly voted yesterday in favor of allowing the arthritis painkiller Vioxx back on the market under strict conditions. The committee also voted in favor of allowing Celebrex and other drugs in the COX-2 class to remain available.
But a substantial majority of the 32-member panel recommended steps to significantly restrict their use and called for extensive new testing of similar arthritis drugs on, or coming to, the market.
The proposed restrictions include a ban on direct-to-consumer advertising, the inclusion of a strong warning in a highlighted black box on the bottle label or box, and a requirement that patients be given a written warning that the drugs increase the risk of heart attacks and strokes. Some members also said the drugs should be used only when other medications have failed.
The panel's message, Chairman Alastair J.J. Wood said, is that issues raised by the COX-2 drugs are "extremely complex" and that "there are no black-and-white answers." But he said that although the group clearly believes drugs used to treat chronic pain are valuable, the drugs need substantially more testing and should not be aggressively advertised, as they had been until last fall.
Although the votes supported controlled marketing of the drugs, the sometimes sharply divided panel hardly gave them a vote of confidence. The votes came only after the advisory group agreed unanimously that COX-2 inhibitor drugs "significantly increase" the risk of heart attacks and strokes.
The FDA usually follows advisory panels' recommendations but is not bound by them. The agency is expected to make its decisions within weeks.
Celebrex and Vioxx were approved in the late 1990s and were aggressively advertised as breakthrough treatments for arthritis. Millions of patients began taking them, although studies have shown that many were not at risk for the gastrointestinal problems sometimes caused by older painkillers, which the newer drugs were designed to avoid.
In addition to voting on whether the COX-2 drugs should remain available to U.S. consumers, the panel was asked to assess the safety of nonsteroidal anti-inflammatory drugs such as Mobic and ibuprofen. The group overwhelmingly recommended that they, too, carry new warnings, although there was a consensus that some of them -- naproxen in particular -- are much safer than others. (Ibuprofen is sold as a generic drug and by the brand names Advil and Motrin; naproxen is sold under brand names including Aleve and Naprosyn.)
Just before the voting began, Wood told the group that it was struggling with the biggest and most complicated drug safety issue to come before the FDA. He said that of the 16 drugs the FDA has taken off the market, none had affected nearly as many people because they involved relatively rare side effects and not a general cardiovascular threat.
The vote to allow Merck & Co.'s Vioxx back on the market was 17 to 15. Vioxx was withdrawn in September, and significant obstacles remain to any return to pharmacy shelves.
For Pfizer Inc.'s Celebrex, the vote was overwhelmingly in favor of keeping it available. A third arthritis medication, Pfizer's Bextra, also won the support of the panel, but by a small majority.
The restrictions proposed by the panel, if adopted by the FDA, will make COX-2 drugs much harder for manufacturers to sell and for patients to obtain. Once the FDA gives a drug a black-box warning, certain kinds of advertising are no longer allowed and doctors tend not to prescribe it widely.
Still, the Vioxx vote in particular was a vindication of sorts for Merck, which withdrew its product in September because of safety concerns. At the time, the company said it believed Vioxx could remain on the market with restrictions, but it decided not to do so because there were alternatives with fewer safety concerns.
The drug's possible path back to the market remains difficult. FDA officials told the panel that if Merck wants to return Vioxx to the market, the company must win new approval for revised label information about safety and how the drug should be used.
Merck officials said that they are open to returning the drug to the market and that "we look forward to discussions with the FDA" regarding Vioxx and other COX-2 products in the pipeline.
On Thursday, Merck Research Labs President Peter S. Kim said his company will reexamine its decision to withdraw Vioxx if the panel concludes that all COX-2 drugs pose cardiovascular risks. He reasoned that if all are potentially harmful, it is appropriate to measure each in terms of both its relative benefit and its risk. Vioxx is the only COX-2 drug that the FDA has found to protect against gastrointestinal damage, the most common side effect of aspirin and the older nonsteroidal inflammatory drugs.
Sen. Charles E. Grassley (R-Iowa), who has been highly critical of the FDA's handling of Vioxx, commended the panel for its "respect for the scientific process."
But he also said: "I remain troubled by the FDA's reluctance to be fully transparent. . . . Specifically, the FDA should value the science of its own employees at least as much as the science presented by drug companies."
In its recommendations on restrictions, the panel made it clear that it thought they should be tightest on Vioxx -- which showed the most significant cardiovascular problems in recently stopped clinical trials.
The FDA convened the extraordinary three-day meeting to solicit recommendations from some of the top experts in the nation on arthritis treatment and overall drug safety. The meeting was called because of the Vioxx withdrawal and similar health concerns linked to Celebrex and Bextra.
Although the panel members were convinced that the COX-2 drugs carry increased risks of heart attacks and strokes, they voiced differing views on how much the drugs benefit patients and whether they are significantly safer than older anti-inflammatory drugs, such as ibuprofen and aspirin. Also weighing on the panel was public testimony Thursday, when many arthritis sufferers pleaded to be allowed to continue using COX-2 drugs.
In a news conference after the votes, John Jenkins, director of the FDA's Office of New Drugs, said the agency will give great weight to the recommendations and comments of the panel. But he said the narrow margins of some votes mean the agency must look carefully at the members' comments.
"Close votes are very challenging to interpret," he said.
Merck shares surged $3.76, or 13 percent, to close at $32.61 yesterday on the New York Stock Exchange. Pfizer shares gained $1.74, or 6.9 percent, to finish at $26.80.
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