Posted on 10/18/2004 11:51:04 PM PDT by neverdem
Less than three weeks after Merck withdrew its arthritis painkiller Vioxx from the market because it increased the risk of heart attacks, Pfizer announced plans yesterday to test if its best-selling painkiller Celebrex, which is in the same class of drugs as Vioxx, can do the opposite - help prevent heart attacks.
But Pfizer's announcement is raising questions.
For one, Pfizer warned only last Friday that Bextra, another of its drugs in the same class as Vioxx and Celebrex, increased the risks of heart attack and stroke in patients undergoing coronary-bypass surgery. So the timing of the announcement of the new Celebrex trial could divert attention from the warning about Bextra.
Another question is whether the new trial would be ethical and able to attract participants, given the problems associated with Vioxx and with Bextra.
"I would not put any of my patients who are at high cardiovascular risk on any drug that is a member of this class based on the current evidence," said Dr. Garret A. FitzGerald, a cardiologist and pharmacologist at the University of Pennsylvania.
Dr. FitzGerald has been a leading proponent of the view that all the drugs in Vioxx's class, known as COX-2 inhibitors, have the same potential risks because of a common mechanism in their action. The new data about Bextra "renders the evidence that this is a class effect overwhelming," he argued.
Pfizer said it planned to test Celebrex in comparison with a placebo in 4,000 patients with osteoarthritis who have recently had a heart attack. Dr. Gail Cawkwell, Pfizer's medical team leader for Celebrex, said numerous studies had shown that Celebrex, which had worldwide sales of $1.5 billion in the first half of this year, did not carry the same risk as Vioxx. In addition, she said, there have been some small studies showing that Celebrex could help reduce cardiovascular risk.
Dr. Cawkwell said Pfizer announced the trial yesterday "because we are really ready to start the study." But given the concerns about Vioxx, she said, the company would first discuss the design of the trial with the Food and Drug Administration and regulators in other countries.
Dr. Janet Woodcock, acting deputy commissioner for operations at the F.D.A., said in a speech at the American College of Rheumatology meeting in San Antonio yesterday that "at this point we don't have any definitive evidence" that the COX-2 inhibitors as a class are more risky than older painkillers like ibuprofen and naproxen. While not referring specifically to the coming Celebrex trial, she said that any clinical trial of COX-2 drugs in patients at high risk of cardiovascular problems "needs careful scrutiny" with regard to ethics.
An expert who supports the trial is Dr. Eric J. Topol, cardiology department chairman at the Cleveland Clinic, who has been a leader in warning of the risks of COX-2 drugs.
"There is potential for benefit," from Celebrex, Dr. Topol said. "There is potential for harm, too. There are hundreds of thousands, if not millions of people with coronary disease who are taking Celebrex today. This would be a big step toward telling if it is helping them or harming them."
COX-2 inhibitors block an enzyme in the body called cyclooxygenase-2, which contributes to inflammation and pain. Since inflammation is a contributor to heart attacks and strokes, blocking it could be helpful in preventing such events. However, there is also evidence that the COX-2 enzyme helps retard blood clotting, so inhibiting it might contribute to the clots that cause heart attacks and strokes.
Besides questions about the new trial, there are also questions about why Pfizer did not disclose the data on Bextra earlier. Dr. Cawkwell acknowledged that Pfizer knew the results of the Bextra trial in bypass patients two months ago.
But the company remained silent about these results, even after Vioxx was withdrawn from the market on Sept. 30. Instead, Pfizer insisted that Vioxx was unique and that there was no evidence of a class effect.
"I think one could only characterize their response to the Vioxx story, where they publicly dismissed the possibility of a class effect, as deceptive," Dr. FitzGerald said.
Dr. Cawkwell said Pfizer wanted to give the results first to investigators in the trial, which it did a couple of months ago. Then it was preparing a scientific publication to inform a broad range of doctors. But given current concern, she said, the company decided to release the data even before the scientific publication.
Dr. Cawkwell said there was no urgency to announce the findings about Bextra when Vioxx was recalled because Pfizer thought that most patients switching off Vioxx would move to Celebrex. But the company is now seeing that a significant number of Vioxx users are moving to Bextra, which had sales of $545 million in the first half of this year, so it made the data public to help patients and physicians decide, she said.
In trading yesterday, Pfizer's shares rose 50 cents, closing at $29. Merck was up 40 cents, to $30.90.
Dr. Cawkwell said the Bextra results in coronary-bypass patients were not indicative of the risk for the broader population. "The setting is so unique that it may or may not be applicable," she said.
Pfizer has said that data so far do not show an increased risk of heart attacks for Bextra users with osteoarthritis or rheumatoid arthritis, or those undergoing general surgery.
But Dr. FitzGerald said that problems seen in bypass patients might also occur, though at a lesser rate, in patients with less cardiovascular risk.
Merck, meanwhile, presented more detailed data from the study that led to the withdrawal of Vioxx. The results were presented at the San Antonio conference, which added a special session at the last minute as Merck hurried to get the data ready.
According to the more detailed data presented last night, 30 patients of 1,287 who took Vioxx had a cardiac event, like a heart attack, compared with 11 of 1,299 on the placebo. There were four deaths from cardiac events in both the Vioxx group and the placebo group. Some 15 patients on Vioxx had a stroke or a transient ischemic attack - sometimes called a ministroke - compared with 7 on the placebo.
New data will be presented in San Antonio today on Arcoxia, a new COX-2 inhibitor being developed by Merck. According to an abstract on the conference's Web site, there was no difference in serious side effects between the patients who took Arcoxia and those taking declofenac, an older painkiller. The study involved 7,111 patients with osteoarthritis who had taken the drug for an average of about nine months.
The F.D.A. is scheduled to decide whether to approve Arcoxia by the end of this month. Many analysts expect it to delay approval until data on longer-term use becomes available. In the Vioxx study, the higher risk of heart attacks and strokes was not seen until patients took the drug for 18 months.
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Interesting. Thanks for the ping.
Thanks for the ping. I'm in my forties but have mucho arthritis in my hands. So far Tylenol takes care it but nice to see I may have other future options.
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