On April 7, 2005, the U.S. Food and Drug Administration (FDA) asked Pfizer, Inc., to remove its Cox-2 inhibitor, BEXTRA, from the market. Pfizer recalled BEXTRA, citing the potential for increased risk of heart attack and stroke. While sound evidence exists that BEXTRA also causes severe forms of skin disorders, including Stevens Johnson Syndrome (SJS) in patients taking the drug, Pfizer denied the recall was based upon these adverse skin conditions.
The FDA decision was contrary to the finding of the FDA Advisory Committee in February of 2005, where the vote supported BEXTRA remaining on market with strong cardiovascular warnings. Reports of undisclosed financial interests of Advisory Committee members that would have substantially affected the outcome if those persons had voted otherwise may have had some effect on FDA's ultimate decision. While outsiders are not privy to the internal FDA discussions, it is rare for FDA to take a position contrary to an Advisory Committee recommendation. What is public information is that the majority of the data before FDA and in the medical community supported that those patients taking Bextra were at increased risk of suffering a heart attack, stroke or other cardiovascular event, and that there was a general lack of demonstrable evidence of an efficacy and safety advantage for Bextra compared with other traditional nonsteroidal anti-inflammatory drugs (NSAIDs).
It is unclear how this will impact the ongoing VIOXX litigation, but certain issues in the case are specifically addressed by the FDA decision. First, Merck has steadfastly asserted that Cardioprotective propensities of the over-the-counter NSAID NAPROXEN reasonably explained the difference in cardiovascular events in VIOXX users in Merck's earlier randomized clinical trial, VIGOR. While asking Pfizer to pull BEXTRA, FDA also asked the manufacturer of NAPROXEN to include cardiovascular warnings on its product. Thus, Merck's position on NAPROXEN remains untenable. Second, BEXTRA has a similar selectivity for Cox-2 and efficacy profile to VIOXX, and these factors should be a strong indication to Merck that FDA will not favorably consider the reintroduction of VIOXX on market or the approval of ARCOXIA, Merck's second-generation Cox-2 NSAID. Merck was never able to show that VIOXX was safer or more efficacious than other NSAIDs on measures of overall safety, and no such data has been made public to indicate that ARCOXIA is any different. For Pfizer, a difficult task will be explaining why the evidence on the cardiotoxicity of Cox-2 NSAIDs was not sufficient for BEXTRA to be voluntarily withdrawn from market far earlier than April 7, 2005.
BEXTRA was on market for approximately 3.5 years, but did not have as significant a market share as VIOXX. Still, sales indicate a large number of persons were prescribed BEXTRA. Pfizer generated about 1.3 billion dollars in sales on BEXTRA for 2004. For attorneys who are reviewing new BEXTRA cases, the literature supports an additional injury to screen for than with VIOXX. Specifically, screen in adverse skin reactions such as Stevens Johnson Syndrome (SJS), which is an extreme allergic reaction. This is different than VIOXX because BEXTRA and CELEBREX are sulfa-containing drugs. There were some SJS warnings placed on BEXTRA in November of 2002, approximately one year after market approval. Stronger SJS warnings were issued by FDA in February of 2003 and through recommended label changes in August of 2004. Despite the growing severity of the problem, Pfizer never put a black-box on the label, which would have killed direct to consumer marketing. For the cardiovascular cases, The New England Journal of Medicine (NEJM) reported on December 23, 2004 that BEXTRA increased the risk of serious cardiovascular outcomes by a factor of approximately three; Circulation reported on January 5, 2005 that BEXTRA was associated with a three-fold higher risk of cardiovascular events than placebo; the Wellpoint Study found that BEXTRA patients had a significant increased risk for heart attack and stroke; and the NEJM published the results of Pfizer's clinical trial on March 17, 2005, confirming the three-fold risk of heart attack and stroke. On November 9, 2004, Dr. Garret A. Fitzgeral, a cardiologist and pharmacologist at the University of Pennsylvania, presented the preliminary results of his BEXTRA study at the American Heart Association meeting in New Orleans, LA, and described BEXTRA as "a time bomb waiting to go off." Just as significantly, on November 109, 2004, the New York Times quoted Dr. Curt Furberg as stating that he and Dr. Fitzgerald's study "showed that BEXTRA is no different than VIOXX, and Pfizer is trying to suppress that information." Sales of BEXTRA did increase after VIOXX was withdrawn from market on September 30, 2004, and it remains to be seen whether the profits to Pfizer were really worth the continuing injury to consumers or the damage to its reputation by continuing to refuse to pull BEXTRA in light of the risks.
BEXTRA securities and ERISA litigation has been ongoing since November in New York, Pfizer's home base. The first BEXTRA personal injury case was also filed in New York at the same time that a consumer class action was filed in Southern Illinois. Multiple federal claims have been filed around the country since that time. A federal MDL has been requested to consolidate all Pfizer Cox-2 NSAID cases and should be heard before the MDL Panel sometime this summer.
There is a Cox-2 NSAID Litigation Group at ATLA with more than 400 current members and there are information packets available for VIOXX, BEXTRA and CELEBREX on the ATLA Exchange.
By: Shelly A. Sanford, TX, and Kristian Rasmussen, FL