Merck pulls Vioxx, cites side effects

Clinical trial of painkiller finds higher risk of heart attacks, strokes

October 01, 2004|By Julie Bell and Ivan Penn | Julie Bell and Ivan Penn,SUN STAFF

Merck & Co. pulled its blockbuster painkiller Vioxx from the market yesterday after identifying an increased risk of heart attacks and strokes, sending its stock into a tailspin and prompting patients to begin switching to alternatives as pharmacies cleared the drug from shelves.

Earlier studies had raised questions about the cardiovascular side effects associated with Vioxx, which the Food and Drug Administration approved in 1999 after concluding that tests showed it was safe and effective for treating osteoarthritis symptoms and pain.

But the full risks often aren't known until drugs are on the market, and Merck said that was what happened in this case.

The company said three years' worth of data from a clinical trial it has now halted led to yesterday's action. The study was designed to evaluate whether Vioxx also is effective in preventing recurrence of polyps in the colon.

The trial was halted after results indicated that patients who took Vioxx for at least 18 months faced twice the risk of heart attack compared with those taking a placebo, though the FDA said the risk for both groups remained small.

"We are taking this action because we believe it best serves the interests of patients," said Merck's chairman and chief executive, Raymond V. Gilmartin.

Merck executives believed it would have been possible to continue marketing Vioxx by putting new warnings on the label. But, "given the availability of alternative therapies, and the questions raised by the data," Gilmartin said, "we concluded that a voluntary withdrawal is the responsible course."

Dr. Steven Galson, acting director of the FDA's Center for Drug Evaluation, said the agency was "interested" in possibly requiring longer studies for similar drugs before approval. The agency said it would monitor similar drugs, including Celebrex and Bextra, for side effects and is likely to seek more data from their manufacturer, Pfizer Inc.

About 2 million people in 80 countries take Vioxx, which posted $2.5 billion in worldwide sales last year - 11 percent of Merck's $22.5 billion in revenue.

The announcement pushed Merck's shares down $12.07, or 27 percent, to close at $33, erasing $28 billion in market value and pulling other stocks down with it.

Patients inundated some physicians with calls and e-mail seeking advice, and some university medical centers put clinical trials involving similar drugs under review, actions that could lead to a halt to those trials.

"I think we're going to have to put them on hold," said Dr. Bruce Smith, a rheumatologist who chairs one of several ethics boards overseeing human trials at Thomas Jefferson University Hospital in Philadelphia.

Smith was referring to all clinical trials involving so-called Cox-2 inhibitors, which, like Vioxx, work by blocking an enzyme that is important in the process of inflammation. The best-known others are Pfizer's Bextra and Celebrex.

All were heralded when they came to market as relatively free of side effects such as gastrointestinal ulcers, of which many patients complained when taking other nonsteroidal anti-inflammatories such as ibuprofen or naproxen.

But in June 2000, Merck submitted a study to the FDA that found an increased risk of heart attacks and strokes in patients taking Vioxx compared with patients taking naproxen. The FDA took the issue to an advisory committee in February 2001 and added warnings to Vioxx's label in April 2002.

Since then, Smith said, he has warned patients to whom he prescribed Vioxx of possible side effects. While he says it may be unethical to continue exposing patients to Cox-2 inhibitors if they are subjects in clinical trials and not technically being treated for anything, he plans to continue prescribing Celebrex and Bextra. He switched at least eight patients yesterday.

Dr. Raymond H. Flores, a rheumatologist at the University of Maryland Medical Center, said the studies he has reviewed do not suggest that Celebrex or Bextra present the same level of risk.

"It makes you wary about using them," he said of Cox-2 inhibitors in the wake of Merck's Vioxx withdrawal, "although my intent is to continue to do so."

Ann Fisher, 43, of Baltimore, who has suffered from rheumatoid arthritis for nearly 20 years, has taken Vioxx almost since it hit the market in 1999. Now, she will have to switch.

The secretary at Mercy Medical Center had been on and off other, more traditional anti-inflammatories over the years, but they gave her stomach problems.

When I went on the Vioxx, the stomach problems stopped, said Fisher, who takes two other drugs to keep her arthritis in check.

"[With] the combination that I'm on now, my arthritis is in total control, and I'm better now than I've ever been," she said. "It's just disheartening to hear that they are going to pull Vioxx, to recall it, because I'm one of the ones who have not had any problems, and it's helped me."

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