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Testimony on the Dangers of Cox-2 Drugs

Testimony of Sidney M. Wolfe, M.D., Director
Public Citizen’s Health Research Group

Before FDA Arthritis and Drug Safety Advisory Committees
Concerning the Dangers of COX-2 Drugs

Four years ago, I testified before this committee that the U.S. Food and Drug Administration (FDA) should require a black box warning on Vioxx and Celebrex because of statistically significant evidence from the Vigor study and trends in the CLASS study of increased cardiovascular risk. An FDA medical officer then properly derided Merck’s explanation that it was naproxen protection, not Vioxx cardiac toxicity, that was responsible for the four-fold increase in myocardial infarction.

What neither the FDA, the advisory committee, nor I knew then was that in 2000, Pfizer had finished a placebo-controlled study using Celebrex to prevent progression of Alzheimer’s disease and that that study had found increased cardiovascular risks for the drug. What I did not know several weeks ago when, having found the still-unpublished results of this study on the PhRMA website, I made the results public, but have just learned, was that although Pfizer withheld the results from the FDA long enough so they were not discussed at that February 2001 meeting, Pfizer forwarded the results to the FDA in June 2001 and, as mentioned yesterday by FDA’s Dr. Witter, the IND for that use of Celebrex was discontinued in July 2001. The FDA was concerned enough about this study that it was presented internally at a meeting in 2001 but never revealed to the public by the agency until yesterday in Dr. Witter’s presentation, which acknowledged that in almost every type of adverse cardiovascular outcome, the cases occurred mainly in those using Celebrex (a total of 3 cardiovascular deaths, non-fatal heart attacks, strokes, heart failure or angina out of 140 patients in the placebo group and 20 such events out of 285 in the Celebrex group). Pfizer’s misleading and undocumented  explanation yesterday that these differences could be explained by differences in baseline characteristics between the groups is belied by the analysis of the APC study on the cardiac risks of Celebrex showing that ”formal statistical tests of interaction showed no differential [cardiovascular] effect of celecoxib with respect to baseline cardiovascular risk”.[1]

Yesterday’s demonstration of the extent to which Pfizer will prevaricate, a form of lying, suggests that behind closed doors even more of this has gone on. If Pfizer representatives had testified under oath yesterday, they might well have been found to have committed perjury. I recommended today to the U.S. Attorney’s Office in New Jersey that they start an investigation of Pfizer for fraud if they have not already begun to do so. I also spoke with Senator Grassley’s office today and requested an investigation concerning FDA’s dangerous suppression of data from this study for more than 3 ½ years.

During the past 33 years, HRG has formally petitioned the FDA to ban a total of five NSAIDS (benoxaprofen-Oraflex, phenylbutazone-Butazolidin, oxyphenylbutazone-Tandearil, suprofen-Suprol and piroxicam-Feldene). As of now, the only one still on the market is the highly gastrointestinal-toxic Pfizer drug Feldene  but the number of prescriptions filled for that drug last year is less than 25% of the eight million prescriptions filled in 1984. Our petition last month to ban Celebrex and Bextra brings the number of such petitions to seven, and it is the responsibility of your two advisory committees and the FDA to add these two drugs to the list of NSAIDs discarded because of the absence of unique benefits and the presence of clear, unequivocally unique risks.

Given that Celebrex and Bextra are making an important contribution to the estimated 100,000 deaths and 2.1 million serious injuries a year from adverse drug reactions, I hope you will recommend a ban of these two drugs. Label limitations to short-term use will fail just as they did with the now-banned NSAID, Duract.

[1] Solomon et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. New Eng J Med 2005;352.