The Vioxx withdrawal is one of those pains that just won't go away. Doctors are in a quandary and many patients who had come to rely on Vioxx and related drugs are having trouble finding a satisfactory replacement. Manufacturer Merck's profits have plummeted and regulators around the world are considering what to do next.
Merck withdrew the drug September 30 after a study showed that prolonged usage could double the risk of heart attack and stroke. That left about 1.3 million Americans looking for a substitute.
Unfortunately, the most likely substitutes -- Pfizer's Celebrex and Bextra -- are also under a cloud of suspicion. All three drugs are a new category of painkiller called COX-2 inhibitors. They're said to be superior to aspirin-type, anti-inflammatory drugs because they're less likely to cause gastrointestinal bleeding and many patients find them more effective at relieving the pain of arthritis and other chronic disorders.
Researchers say the number of patients who have had heart attacks or strokes as a result of taking Vioxx could range from 30,000 to 100,000. That does nothing to comfort patients who have few side effects clearly traced to Vioxx.
"I took Vioxx for about 2 years and now am very concerned with my future health," Denise of Omaha said in a complaint to ConsumerAffairs.com. "At this point I have occasional chest pains and heart beat skips once in a while."
Doctors are also looking for solutions, now that another "miracle" drug has fallen from its pedestal.
"I had a lot of patients on Vioxx. In some cases, it was the only thing that worked for them," said Dr. John Givogre, a Gainesville, Ga., pain management specialist quoted in the Gainesville Times.
The American Medical Association has cautioned physicians to think twice before prescribing any COX-2 medication. But Givogre said he's switched many of his patients to Celebrex or Bextra despite the warning. He said there's no firm evidence of increased cardiovascular risk in other COX-2 drugs.
Merck
The sudden withdrawal of one of its top-selling drugs is a financial cataclysm for Merck. The company says it has lost $553 million in profits from lost sales and, even worse, faces a mountain of lawsuits that could bankrupt the company.
Merck has been hit with at least 300 lawsuits so far from former patients alleging various side-effects, and it also faces shareholder lawsuits. Merck said it thinks it has liability insurance of up to $630m, although it admits that some of its insurers are disputing this.
Merck, based in Whitehouse Station, N.J., yesterday said its net income slumped 29 percent to $1.33 billion, or 60 cents per share, from $1.86 billion a year earlier.
Pfizer
Hoping to counter negative reaction to COX-2 drugs, Pfizer is planning to sponsor a major clinical study to further assess its COX-2 medication Celebrex in osteoarthritis patients at high risk for cardiovascular disease.
This study is part of a larger CV exploration program with Celebrex that started over 18 months ago. This newly announced clinical trial, which will be conducted at major universities and hospitals around the world, is expected to start early in 2005. Due to recent questions raised about the cardiovascular safety of the COX-2 specific inhibitors, Pfizer will be discussing the study design with the FDA and other regulatory agencies prior to finalizing its details and start date.
Pfizer officials say they remain confidence in the safety of Celebrex, pointing to "the substantial body of experience" gained in several trials.
"In fact, small mechanistic studies suggest that Celebrex's anti-inflammatory properties as well as additional unique Celebrex-specific characteristics may improve vascular function in patients with established coronary artery disease. That is why we feel it is important at this time to announce our plans to conduct the first large-scale clinical study involving the use of a COX-2 specific inhibitor to look at inflammation and CV events in osteoarthritis patients at high risk for cardiovascular disease," said Dr. Joseph Feczko, MD, president of worldwide development at Pfizer.
The study will enroll more than 4,000 patients around the world who have had a recent heart attack and who also have a history of osteoarthritis. The study will assess the effects of Celebrex on inflammation and cardiovascular (CV) events. The multi-center, randomized, placebo-controlled study will be conducted over a period of at least two years and will include rigorous monitoring of cardiovascular safety by an independent data safety monitoring committee, the company said.
Pfizer said more than 27 million patients in the U.S. have been prescribed Celebrex, which was approved by the U.S. Food and Drug Administration in 1998. It says patients treated in clinical studies of up to 4 years show no increased CV safety concerns.
Regulators Ponder
The European Commission has ordered a full-scale probe into the safety of the remaining COX-2 drugs. The London-based European Medicines Agency said on Friday it had been given the go-ahead for the investigation after a preliminary review established there were serious safety questions.
The European review will include Novartis AG's new COX-2 drug Prexige, now on sale in Britain and Australia but not yet approved elsewhere in the European Union or the United States.
The U.S. Food and Drug Administration (FDA) is planning an advisory committee to review the safety of the COX-2 drug class in January 2005.
