PSA Rising, February 18, 2004. Two months after the National Cancer Institute shut down a clinical trial investigating Celebrex to prevent a rare type of colon cancer polyps, a panel of health advisors has told the Food and Drug Administration (FDA) to allow the painkiller to stay on the market.
Celebrex was called in question when it was learned that in a colon polyp prevention trial patients who took the drug had dose-related increased risk of cardiovascular events including death from heart attack and stroke.
Patients who took 400 mg. of Celebrex twice daily for more than two years had a 3.4 times greater risk of serious cardiovascular event (fatal or non-fatal) compared to placebo. Patients who took 200 mg. of Celebrex twice daily had two and a half times higher risk of these cardiovascular problems.
Celebrex came under scrutiny just months after it emerged that Vioxx, another COX-2 inhibitor painkiller drug, doubled the risk of herart attack and stroke in people using to control arthritis pain. Merck took Vioxx off the market voluntarily in early September 2004. This "voluntary recall," which did not deter personal injury and class action law suits, shook the market and led to scrutiny of all COX-2 inhibitors and some older-style painkillers like Aleve (Naproxin) and Ibuprofrin.
People with arthritis suffered a huge blow when Merck withdrew Vioxx and doctors began questioning Celebrex and Bextra (another druig in the same class). Many cancer patients also have been affected -- not only patients at risk for the rare colon polyp disease. Celebrex, in small clinical studies, had begun to look useful against prostate cancer. Many men battling prostate cancer receive prescriptions for Celebrex from oncologists who see evidence that this class of drugs, the COX-2 inhibitors, may prevent or slow down disease recurrence.
The FDA must soon decide whether to ban Vioxx, Celebrex and Bextra, or to let all three stay on the market (if the manufacturers wish), or whether to distinguish among the three. After today's panel vote, Dr. John Jenkins, director of the Office of New Drugs at the F.D.A., said the panel had made clear "that they felt that these agents should maybe not be as widely used."
Today most members of the panel assembled to advise in this decision took account of how valuable these drugs are to patients needing pain-control. The agency should not ban any of these drugs, the panel said. But in view of the heart risks, which exist for heavy use of almost painkiller but are evidently higher for these COX-2 inhibitor drugs, the panel said the FDA should do three things:
- place "black box" warnings on the drugs' labels detailing their heart risks
- ban consumer advertising for the drugs
- require each prescription to include a guide outlining the risks.
According to New York Times reporter Gardiner Harris "The panel voted 31 to 1 that Pfizer should be allowed to continue selling Celebrex, which members said was safer than the other two. The vote on Bextra was 17 to 13 with 2 abstentions, and 17 to 15 on Vioxx."
The FDA is unlikely to ban advertising. Dr. Jenkins said it had no power to do, Harris reports. Whether the FDA will actually make any distinction and come down harder on Vioxx and Bextra than on Celebrex remains to be seen.
Among oncologists prescribing a daily dose of COX-2 inhibitor against prostate cancer, Celebrex seems to be preferred to Vioxx. Pfizer, which makes Celebrex, unlike Merck has opted at times for outright denial that its drug harms the heart. Pfizer's presentation to the advisory panel "did not include any information about a large federally sponsored trial in which patients taking Celebrex had more than three times as many heart attacks as those given a placebo," Harris reports.
"You're telling us that you don't have data that you published two days ago in The New England Journal?" the panel's chairman, Dr. Alastair Wood, asked.
Sales for Celebrex last year totaled $3.3 billion, and those for Bextra totaled $1.3 billion.
J. Strax, February 18, 2004
