The Duract debacle today may have a negative effect on all biotech stocks, but it's worth noting that any future pressure that might be put on the FDA to go back to the old, longer drug-approval process will be for "me-too" drugs, that is to say, drugs that are coming to market where effective medicines for that particular ailment are already available. HU-211 is not in this category because no effective single treatments are available for brain trauma.
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<<NYTimes, June 23, 1998
F.D.A. Withdraws Second Drug in Two Weeks, Raising Questions About Speedy Approval
By SHERYL GAY STOLBERG
WASHINGTON -- For the second time in two weeks, the Food and Drug Administration has taken the rare step of pulling a prescription drug off pharmacy shelves, a move that is renewing questions about whether the agency's new emphasis on speeding up drug approvals is allowing unsafe medicines to reach patients.
The drug, Duract, a painkiller manufactured by Wyeth-Ayerst Laboratories of St. Davids, Pa., has caused a dozen cases of serious liver failure since it went on the market last July, including those of four patients who died and eight who required liver transplants. All cases involved patients who took the drug for longer than the recommended 10 days.
Both the agency and the company are advising patients who have been taking Duract for longer than 10 days to stop immediately; all patients who are using the medication should consult their doctors.
The announcement on Monday was the third time in nine months that the food and drug agency removed a new medicine for safety reasons. On June 8, the high blood pressure medication Posicor was banned because it turned out to be potentially lethal when used in combination with a long list of other drugs. Last September, the popular diet drug Redux was taken off the market, along with its close cousin, fenfluoramine, when both were implicated in heart valve problems.
"This is the worst record we have ever had -- it's unprecedented," said Thomas Moore, a senior fellow in health policy at George Washington University Medical Center who studies drug safety. "I believe we are paying the wages of the one-sided debate that we have had in this country that the speed of FDA approval is the only issue."
It is extremely unusual for the FDA, which is widely regarded as the most safety-conscious consumer protection agency in the world, to have to withdraw a drug once it has been approved. Including the most recent withdrawals, there have been only six such withdrawals in the past decade, according to Dr. Murray Lumpkin, deputy director of the agency's Center for Drug Evaluation and Research.
In recent years, however, the agency has been under intense pressure from congressional Republicans to speed up its drug approval process, and it has given its imprimatur to a record number of new drugs, 92, over the past two years. That fast-track approval process has been financed in large part by the pharmaceutical industry, which gave the FDA $327 million in user fees between 1992 and 1997. The money was used to hire 600 new employees to review drug applications.
Proponents of the fast-track system argue that it is necessary to bring life-saving therapies to patients who desperately need them. However, Lumpkin estimates that only 20 percent of the new medicines approved fall into the category of breakthrough drugs. The rest, including Duract and Posicor, are what is known as "me-too drugs," medicines that treat disorders for which there are already plenty of approved therapies, leaving critics to wonder why they are allowed on the market in the first place.
"The agency has been put under too much pressure to approve more drugs faster, whether they are needed or not," said Larry Sasich, a pharmacist for Public Citizen's Health Research Group, a Washington advocacy organization. "This is the price that the American public is paying for believing that the FDA was keeping life-saving medicines out of the hands of the American public, which is simply not true."
Lumpkin, however, defended the agency, saying the review of Duract took nearly three years and was extremely thorough. Although the agency was aware of the potential for liver problems with long-term use, he said, it made a calculated decision to approve the drug for short-term use, no more than 10 days, because the benefits outweighed the risks.
"This was not a rushed decision by any means," Lumpkin said, adding that the agency still believes the drug is safe and effective when used for fewer than 10 days. "There is nothing in our data that makes you think that if you used this product as labeled it would be unsafe."
But Sasich wondered why the FDA approved Duract in the first place, given that there are plenty of other drugs on the market to treat pain. "This was a drug that no one needed," he said. "It's the same scenario as we went through with Posicor."
During the 11 months that Duract was on the market, it was prescribed to 2.5 million people, according to the manufacturer, Wyeth-Ayerst, a division of American Home Products Corp. Dr. Philip deVane, the company's North American medical director, said that 15 percent of the prescriptions were written for longer than 10 days, despite clear warnings on the label.
The drug, which goes by the generic name bromfenac, belongs to a class of medications known as nonsteroidal anti-inflammatory drugs, or NSAIDS. In addition to treating pain, these drugs, some of which are so safe they can be sold over the counter, are often used for chronic conditions such as rheumatoid arthritis. Experts say patients typically take NSAIDS for weeks or months at a time, which may explain why doctors continued to prescribe Duract for long times.
Duract went on the market last July, and by this February, deVane said, Wyeth-Ayerst had received three reports of liver injuries to patients who were taking the drug for longer than 10 days. At the FDA's request, the company then put a black box on Duract's package to highlight the warning against extended use.
But when the food and drug agency continued to receive reports of liver trouble, including the four deaths, Lumpkin said, officials decided that the risk was no longer worth the benefit.
"When there are other alternatives that don't have this kind of serious reaction over long-term use, there is no reason to take the risk," he said. The FDA then asked the manufacturer to withdraw Duract, and the Wyeth-Ayerst complied, describing the decision as voluntary.
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