Merck & Co. voluntarily withdrew its blockbuster arthritis drug Vioxx from the market Thursday after a new study showed that it nearly doubled the risk of heart attacks and strokes among people taking it for at least 18 months or longer.
The loss of the drug, which has worldwide sales of nearly $2.5 billion per year, represents a major financial setback for Merck, which lost almost $27 billion in stock market value in a matter of hours.
Physicians recommended that patients taking the drugs -- about 2 million worldwide -- talk to their doctors and switch to other medications. Merck said it would set up a program to buy back unused supplies of Vioxx.
"We are taking this action because we believe it best serves the interest of patients," Merck Chairman Ray V. Gilmartin said in announcing the recall.
Although the timing of the announcement was unexpected, the withdrawal does not come as a complete surprise because "earlier studies had already raised this concern," said Dr. Gregg C. Fonarow, a cardiologist at UCLA Medical Center. "There was already a movement away from Vioxx, but there are still a large number of people being treated with it."
Experts said the risk of life-threatening events was small and that the findings probably did not apply to other members of the class of drugs called Cox-2 inhibitors. Nonetheless, the Food and Drug Administration said Thursday that it would reexamine all similar drugs on the market and could require additional data for new drugs in the same class.
The Merck announcement sent many patients to their physicians in fear for their health and their ability to control severe pain.
"If you get off Vioxx and still have pain, there are five to seven other [drugs] that people need to work their way through to find something that is effective," said Dr. Steven Abramson of the New York University School of Medicine.
The most immediate beneficiary will be Pfizer Inc.'s Cox-2 inhibitor Celebrex, which is projected to have worldwide sales of at least $3.3 billion this year. Pfizer also has a second-generation drug called Bextra, which has projected sales of about $600 million, and Merck has a second-generation drug called Arcoxia that has been approved in 47 countries but is awaiting approval from the FDA.
The FDA had delayed its decision on Arcoxia because of earlier concerns about Vioxx, and the new results seem likely to delay it further and make it more difficult for other drugs of the class to reach the market, experts said.
In particular, the agency seems likely to require longer clinical trials before approval, because the new risks did not develop until after 18 months of use. But the FDA has not decided how it will approach the problem, said John Jenkins, director of the FDA's office of new drugs.
The agency requires trials of six to 12 months for drugs treating chronic diseases, he said, adding that "it is difficult to ask an arthritis patient who has inflammation and pain to remain in a longer-term, placebo-controlled trial."
Steve Galson, acting director of the FDA's Center for Drug Evaluation and Research, said: "I am sure we are going to ask for more data, but I can't tell you exactly what that data is."
Cox-2 inhibitors have been extremely popular since they were first introduced in 1999. Their chief advantage is that, unlike aspirin, ibuprofen and other over-the-counter drugs for inflammation, they do not cause gastrointestinal bleeding. Their principal drawback is cost, about $3 per day, compared with about 3 cents per day for aspirin or ibuprofen.
In the United States, more than 84 million prescriptions for Vioxx have been written since its introduction. Most of the prescriptions are for long-term treatment of the chronic pain and inflammation of osteoarthritis and rheumatoid arthritis, but the drug is also used widely for short-term treatment of many types of pain.
To obtain FDA approval, Merck tested the drug in clinical trials involving 3,900 patients. Although the study found an increase in high blood pressure cases, there was no sign of the drug causing heart attacks. The company's final study required for FDA approval lasted 12 months.
But a 2001 report in the Journal of the American Medical Assn. found signs that the drug might increase cardiovascular risks, and the FDA required a warning on the drug's label.
The new findings came in a three-year study funded by Merck to determine whether Vioxx could retard the progression of colon polyps into full-blown cancer. It is the longest study of a Cox-2 inhibitor that has been conducted so far.
Merck stopped the trial prematurely Sept. 23 when the trial's external data-monitoring board alerted the company to a potential problem. At that point, 25 of 1,299 patients receiving a placebo had suffered a heart attack (1.9%), compared with 45 of the 1,287 patients receiving Vioxx (3.5%), according to a Merck spokesman.
The number of deaths in each group was the same: five.
