We’ll now transition into the detailed accountings of the (alleged) puffery, and hucksterish-tactics that Pharmacia, and later Pfizer, employed to flog the likes of Celebrex®, and Bextra® — to an unsuspecting public (and their prescribing physicians) as pain-relievers, all while in possession of (self-commissioned) study results that strongly suggested the drugs were causing substantially elevated cardiovascular risks in patients on them.
Again, this story is told entirely from public court pleadings in the ongoing federal ERISA “breach of fiduciary duties” class action in the Southern District of New York. Remember that, in each case below, whenever Pfizer is mentioned, the reference would also (from March 31, 2000 — through and including April 16, 2003) ALSO refer to Pharmacia, then controlled by Fred Hassan, and Carrie S. Cox.
[Part I of this series appears here.] Let’s get to it, then:
. . . .Each of the Pharmacia Director Defendants was privy to information at the highest level of Pharmacia. Each of the Pharmacia Director Defendants [including Fred Hassan, and Executive Officer Carrie Cox] knew or should have known the true state of affairs at Pharmacia, the serious and substantial problems related to Pharmacia’s marketing of risky products (including Celebrex and Bextra) and Pharmacia’s liability for injuries allegedly related to those products. . . .
On February 1, 2005, the Boston Globe reported on the 1999 Alzheimer’s study, stating, “Pfizer, Inc, has revealed it completed a study four years ago [then known as Pharmacia] that links its painkiller Celebrex to a ‘statistically significant’ increase in heart problems. The recent disclosure. . . appears to contradict recent statements by the company”. . . .
At no time has the FDA permitted Celebrex to claim increased gastrointestinal safety over traditional NSAIDs or to otherwise maintain superiority in safety or efficacy to such drugs. Beginning with its December 1998 letter approving the Celebrex NDA, the FDA advised Celebrex’s marketers that “promotional activities that make or imply comparative claims about the frequency of clinically serious GI events compared to groups of NSAIDs or specific NSAIDs will be considered false and/or misleading without differences having been demonstrated in adequate, well-controlled studies”. . . .
When all of the CLASS data were considered, most or all of Celebrex’s purported safety advantage disappeared. Six of the seven serious gastrointestinal complications occurring during the second half of the study were in Celebrex users. . . .
The data for the final six months of CLASS became known when Pfizer and Pharmacia appeared before an FDA Advisory Committee considering a proposed GI label change in February of 2001. The results of the CLASS study were also eventually supplied to the FDA’s Arthritis Drugs Advisory Committee (“the Advisory Committee”), which reviewed them at its meeting on February 7, 2001. . . . The Advisory Committee determined that “the sponsor’s presentation of 6-month data. . . are not statistically valid or supportable,” and its gastroenterology reviewer concluded that the first six months of data did not merit separate consideration. Moreover, based on data from the entire year of the study, the Advisory Committee found that “the sponsor has failed to demonstrate a statistically significant lower rate” of serious GI complications in Celebrex as opposed to other NSAID users. In fact, during the second six months of CLASS, the risk of serious GI complications associated with Celebrex appeared to be higher than that associated with “both ibuprofen and diclofenac.” . . . .Celebrex had failed to achieve its primary endpoint of reduced “clinically significant serious gastrointestinal events.” Accordingly, the Advisory Committee recommended that the Celebrex package insert continue to contain the same gastrointestinal warnings as traditional NSAIDs, and advised that further studies be undertaken to assess the risk of COX-2 inhibitors when taken with aspirin.
The medical community condemned. . . Pharmacia’s touting of the CLASS Study results based on partial data rather than the complete data set. Dr. M. Michael Wolfe, a Boston University gastroenterologist who praised the initial CLASS results, said he was “flabbergasted” and “furious” that he had praised a study based on incomplete data, which made him look “like a fool.” In a similar vein, JAMA’s editor, Catherine D. DeAngelis, admitted to being “disheartened to hear that they [Pharmacia] had those data at the time” the manuscript of the article was submitted to JAMA. She stated she was “very upset when I found out that they had a full year’s data.” Likewise, JAMA deputy editor Drummond Rennie stated that Pharmacia, as well as the study’s authors, “were not open with us.” T. Burton & G. Harris, Note of Caution: Study Raises Specter Of Cardiovascular Risk For Hot Arthritis Pills — Vioxx and Celebrex Marketers Dispute the Research, Sought to Downplay It — A Spurned Appeal to JAMA, The Wall Street Journal Aug. 22, 2001 at A1. . . .
[Later] studies confirm[ed] the now well-recognized fact that Celebrex presents an increased risk of cardiovascular injury. A 2006 study reported that Celebrex doubles the risk of heart attack. B. Caldwell, S. Aldington, M. Weatherall, P. Shirtcliffe & R. Beasley, Risk of Cardiovascular Events and Celecoxib: A Systematic Review and Meta-Analysis, J. R. Soc. Med. 2006; 99:132-40 (March 2006). One of the authors of that study, Professor Richard Beasley, told Reuters that the cardiovascular risk was common to the entire class of drugs known as COX-2 inhibitors. . . .
Today, Pfizer’s Celebrex website states: “Important Information: Celebrex may increase the chance of a heart attack or stroke that can lead to death. . . .” On April 7, 2005, in the same press release in which it announced the “black box” label for Celebrex, Pfizer announced that it had been told by the FDA to remove Bextra from the market. Pfizer stated that:
Pfizer respectfully disagrees with FDA’s position regarding the overall risk/benefit profile of Bextra. However, in deference to the agency’s views, the company has agreed to suspend sales of the medicine pending further discussions with the FDA. Pfizer said it will explore options with the agency under which the company might be permitted to resume making Bextra available to physicians and patients. For now, patients should stop taking Bextra and contact their physicians about appropriate treatment options.
In response to the removal of Bextra, drug industry analyst C.J. Sylvester [then] at Banc of America said that Bextra withdrawal took him by surprise, noting it came just two days after Pfizer executives said sales of the arthritis drugs would be reinvigorated in coming months. . . .
FDA has also noted a pattern of Pfizer [then known as Pharmacia] failing to disclose or minimizing the risks of Celebrex. On or about February 1, 2001, the FDA sent a “Warning Letter” citing Pharmacia for minimizing the contraindications and risks associated with Celebrex use and making unsubstantiated comparative claims of its superiority to other NSAIDs. The Warning Letter concluded as follows:
Your promotional activities described above raise significant health and safety concerns in that they minimize crucial risk information and promote Celebrex for unapproved new uses. In two previous untitled letters dated October 6, 1999, and April 6, 2000, we objected to your dissemination of promotional materials for Celebrex that. . . contained unsubstantiated comparative claims, and lacked fair balance. Based upon your written assurance that this violative promotion of Celebrex had been stopped, we considered these matters closed. Despite our prior written notification and notwithstanding your assurances, Pharmacia has continued to engage in false or misleading promotion of Celebrex. . . .
The FDA [earlier] found [that Pharmacia] materials misrepresented the safety profile of Celebrex compared to other NSAIDs, and failed to provide any risk information concerning the use of Celebrex. The marketing materials also contained “several unsubstantiated comparative claims comparing Celebrex to Vioxx. . . .” In addition, in November 2000, the FDA issued yet another letter regarding Celebrex. The FDA told. . . Pharmacia to stop running a TV commercial that suggested arthritis patients could “play in the park” as a result of Celebrex, and “overstate[d] the efficacy” of the drug. . . .
Disgusting. it is abidingly puzzling to me that Mr. Hassan is still in a position of responsibility in the life sciences industry, after the above, and then, while at legacy Schering-Plough, the Vytorin® ENHANCE study delay debacle. And Ms. Cox was right beside him, shovelling coal into the boiler, in each of these aforementioned locomotive train-wrecks.