Merck Withdraws Vioxx From Market Over Safety Concerns

Merck officials on Thursday announced that the company is withdrawing from the market the blockbuster arthritis drug Vioxx after a study "confirmed simmering concerns" that the drug raises the risk of heart attack and stroke, the Washington Post reports. It is the largest voluntary drug recall in history (Kaufman, Washington Post, 10/1).

About two million people worldwide currently use Vioxx, and more than 100 million Vioxx prescriptions have been written since it was introduced in 1999. In 2003, Vioxx had global sales of $2.5 billion (Martinez et al., Wall Street Journal, 10/1). Raymond Gilmartin, Merck's president, chair and CEO, said, "We believe it would have been possible to continue to market Vioxx with labeling that would incorporate these new data. However, given the availability of alternative therapies and the questions raised by the data, we concluded that a voluntary withdrawal is the responsible course to take" (Kaufman, Washington Post, 10/1). The announcement caused Merck's shares on Thursday to fall by 27%, or $12.07, to $33 -- the largest drop in percentage terms for a stock included in the 30-company Dow Jones Industrial Average since September 2001.

Although Merck had been "dogged for several years" by research suggesting the drug increased risks of heart problems, the company "vehemently denied there was a connection" until Thursday's announcement, the Wall Street Journal reports (Martinez et al., Wall Street Journal, 10/1). The data that persuaded the company to recall Vioxx came from a three-year trial designed to determine how effective a standard, 25 milligram dose of Vioxx is in preventing recurrence of potentially cancerous colorectal polyps (Reuters/Washington Post, 9/30).

The study was stopped prematurely on Sept. 23 when the trial's external data-monitoring board notified Merck of results indicating a possible link between Vioxx and heart problems. The data indicate that 45 of 1,287 patients taking Vioxx, or 3.5%, have had a heart attack since taking the drug, compared with 25 of 1,299 patients taking placebos, or 1.9%. Five patients in each group died (Maugh/Gellene, Los Angeles Times, 10/1). Dr. Peter Kim, president of Merck Research Laboratories, said, "What we found in this study is that beginning after 18 months, there was a discernible and unexpected increase in cardiovascular disease rates." He added, "We certainly don't understand the cause of this effect, but it is statistically significant and it indicated that there is an issue" (Kolata, New York Times, 10/1).

When Merck tested Vioxx in 3,900 patients during a 12-month study to receive FDA approval, researchers found an increase in high blood pressure among patients taking the drug, but there was no sign that it caused heart attacks. However, in 2001 -- two years after the drug's market release -- a report in the Journal of the American Medical Association found signs that the drug might increase the risk of cardiovascular disease (Maugh/Gellene, Los Angeles Times, 10/1). Merck added the study's finding to Vioxx's label in April 2002 at FDA's request. Several subsequent studies also found a higher incidence of heart attacks and strokes among patients taking Vioxx, but medical experts differed over the interpretation of the data (Kolata, New York Times, 10/1).

Dr. Steven Galson, acting director of FDA's Center for Drug Evaluation and Research, said that although the agency had been "closely monitoring" reports of serious side effects from Voixx through its national adverse-event reporting system, it has been difficult to attribute heart problems to the drug because so many U.S. residents have heart attacks and strokes (Kaufman, Washington Post, 10/1).

Senate Finance Committee Chair Chuck Grassley (R-Iowa) sent a letter to FDA seeking information about its actions on Vioxx as part of his staff's investigation into FDA's management of safety issues. "Once again, the FDA has remained on the sidelines while life-threatening issues threatened the American public," the letter said. However, John Jenkins, director of FDA's office of new drugs, said agency officials "feel confident, based on the data we had when we had it, we took the appropriate actions" concerning Vioxx (Martinez et al., Wall Street Journal, 10/1).

However, the Vioxx study results are likely to change the way FDA evaluates other Cox-2 inhibitors, according to the Los Angeles Times. Currently, FDA requires trials of six months to a year for drugs treating chronic diseases, but because the heart-related risks did not develop until after 18 months of use, FDA "seems likely to require longer clinical trials " for other drugs of the class before approving them for market, the Los Angeles Times reports (Maugh/Gellene, Los Angeles Times, 10/1). FDA officials said they will begin an additional study of three other Cox-2 inhibitors, which have not been associated with such risks (Kaufman, Washington Post, 10/1).