Problems With Vioxx Were Known Four Years Before Drug Was Withdrawn, New Lancet Study Indicates

The increased risk for cardiovascular events among patients who took Vioxx, a COX-2 inhibitor that Merck withdrew from the market in September, was evident by 2000, according to a study published on Friday in the journal Lancet, the Newark Star-Ledger reports (Silverman, Newark Star-Ledger, 11/5). In the study, Dr. Peter Juni from the University of Berne in Switzerland and colleagues examined 18 randomized controlled clinical trials and 11 observational studies that involved Vioxx (Juni et al., Lancet, 11/5). The 29 studies, conducted prior to 2001, involved 25,273 participants (Harris, New York Times, 11/5). According to the new study, by the year 2000, 52 of about the 20,000 participants who took Vioxx experienced a heart attack -- about two times the number of those who took either placebos or older pain medications. "At the end of 2000, the effect was both substantial and unlikely to be a chance finding," Juni wrote, adding that after the end of 2000, "an increased risk of myocardial infarction was evident." Merck officials have said that although a 2000 study that compared Vioxx with naproxen, an older pain medication, found more cardiovascular problems among participants who took Vioxx, the ability of naproxen to protect the heart might have led to the results. However, according to the new study, "if a protective effect of naproxen exits, it is probably small and not large enough to explain the findings."

Increased Cardiovascular Risk for Short-Term Users
The new study also found that participants who took Vioxx for only a few months had an increased risk for heart attack compared with those who took placebos. At the time Merck withdrew Vioxx from the market, company officials said that they found "no signs of heart problems among patients who took Vioxx for less than 18 months," the Star-Ledger reports (Newark Star-Ledger, 11/5). The study concluded that Vioxx "should have been withdrawn several years earlier" and that Merck and FDA must clarify their decision not to "continuously monitor and summarize the accumulating evidence" (Lancet, 11/5).

Editorial Criticizes Delay in Vioxx Withdrawal
In an editorial that accompanied the study, Lancet editor Richard Horton wrote that the "licensing of Vioxx and its continued use in the face of unambiguous evidence of harm have been public health catastrophes." He added that the study "points to astonishing failures in Merck's internal systems of post-marketing surveillance, as well as lethal weaknesses" in FDA oversight (Newark Star-Ledger, 11/5). Horton concluded that "Merck and the FDA acted out of ruthless, short-sighted and irresponsible self-interest" and called for reforms to the FDA prescription drug safety review process.

Merck, FDA Reaction
Merck officials wrote in a statement that the study was "not comprehensive or new," the Times reports. "Merck was vigilant in monitoring and disclosing the cardiovascular safety of Vioxx, and we absolutely disagree with any implication to the contrary," the statement said (Harris, New York Times, 11/5). Merck also said that the study "failed to include two important studies," the Star-Ledger reports (Newark Star-Ledger, 11/5). Sandra Kweder, deputy director of the FDA Office of New Drugs, said that the allegations Horton made in his editorial were "flat-out wrong" (New York Times, 11/5).

The study is available online.

Plaintiff Attorneys To Meet Next Week
Hundreds of attorneys who represent patients injured or killed after they took Vioxx will meet next week to "lay the groundwork for a nationwide legal assault" against Merck, the Times reports. On Tuesday, attorneys for plaintiffs and Merck will meet informally in Pasadena, Calif., at a conference on Vioxx litigation. On Thursday, about 500 attorneys for plaintiffs will meet in Las Vegas to "compare notes ... on the types of clients who may make the strongest cases, with a premium on people who were in demonstrably good health before taking Vioxx," according to the Times. They also will discuss cooperation in the collection of evidence and expert testimony and consider strategies to influence where most cases are heard after state and federal judges consolidate them (Feder, New York Times, 11/5). Attorneys for plaintiffs said that they have filed at least 700 lawsuits related to Vioxx nationwide. However, Merck officials estimate the number at only 300 (Agovino, AP/Hartford Courant, 11/5). Both Merck and a plaintiff attorney recently asked a panel of judges that supervises mass lawsuits in federal courts to assign the Vioxx cases to one judge. The panel likely will hear arguments on the requests in January (Feder, New York Times, 11/5).

Merck Could Replace CEO Early
Although Merck management and board members have "consistently affirmed that it was the company's long-standing plan to name a successor" to current company CEO Raymond Gilmartin by the end of 2005 and have a transition period through March 2006, "current events could speed up that schedule," the Wall Street Journal reports. Concerns about how Merck has addressed the withdrawal of Vioxx have prompted Merck to "quickly find a successor," according to the Journal. Merck has hired Heidrick & Struggles to conduct a search for a new CEO -- a process that in most cases lasts no longer than six months -- which might indicate that Gilmartin "could step aside as early as the spring, more than a year ahead of the deliberate succession plan," the Journal reports (Hensley et al., Wall Street Journal, 11/5).

Canadian Health Officials Request Safety Data on Celebrex
Officials from Health Canada on Oct. 19 asked Pfizer to submit more safety information on the COX-2 inhibitor Celebrex, which "has been touted as a safer option than Vioxx," after they received more than 100 adverse event reports related to the medication over the past five years, the Wall Street Journal reports. The reports included 19 cases of heart attack, cardiac arrest or heart failure and five cases of stroke, the Wall Street Journal reports (Hovey, Wall Street Journal, 11/4). Canada Adverse Drug Reaction Monitoring Program, a division of Health Canada, collects reports from health care providers and patients and establishes a database that is "meant to serve as a sort of early warning system for safety problems," the AP/Star-Ledger reports (McClelland, AP/Newark Star-Ledger, 11/5). Health Canada officials noted that the reports on adverse events related to Celebrex "are only suspected by the people reporting them, and they don't take into consideration the patients' other medical conditions that could have led to the adverse reaction," the AP/Atlanta Journal-Constitution reports (AP/Atlanta Journal-Constitution, 11/5). Pfizer officials said that they submitted the requested information on Celebrex to Canadian health officials this week (Wall Street Journal, 11/4). They added in a statement, "It is essential to remember that the information provided is uncontrolled and may be second-hand or incomplete." Dr. Patrice Roy, director of scientific affairs for Pfizer Canada, said that Celebrex "has been studied in 30,000 patients, has been prescribed to over 40 million patients worldwide" since the medication reached the market in 1998, adding that "basically, we haven't seen anything" (AP/Atlanta Journal-Constitution, 11/5).