FDA Says No to Vioxx Successor

Mar. 23 -- FRIDAY, April 27 (HealthDay News) -- The U.S. Food and Drug Administration on Friday turned down Merck & Co.'s request to market Arcoxia, a successor to its banned arthritis drug Vioxx.

The decision came as little surprise, since an FDA advisory panel of medical experts had already voted 20-1 against the drug's approval on April 12.

Arcoxia (etoricoxib) is a cox-2 inhibitor, the same class of drugs that includes Vioxx, Bextra and Celebrex. Vioxx was withdrawn from the market in September 2004, after studies showed it doubled the risk for heart attack and stroke. Bextra was withdrawn for similar reasons early in 2005. Celebrex remains on drug store shelves, albeit with a strong warning label highlighting potential heart risk.

But "just having a similar drug in the market is no reason to approve this drug (Arcoxia) or any other similar drug," Dr. Robert Meyer, director of the FDA's Office of Evaluation in its Center for Drug Evaluation and Research, said after the advisory panel's vote.

Meyer told a news conference at the time that the panel wanted any new non-steroidal anti-inflammatory drugs (NSAIDs), which include cox-2 painkillers, to undergo head-to-head comparisons to similar drugs before applying for U.S. approval.

The FDA decision was preceded by a barrage of criticism over Arcoxia's potential risk for increasing heart attacks and strokes, particularly among people with existing heart disease.

Arcoxia is designed to treat the pain of osteoarthritis without the harsh stomach effects associated with painkillers such as aspirin.

But in his testimony before the agency's advisory panel, FDA scientist Dr. David Graham said drug safety studies performed on Arcoxia were neither adequate nor reasonable to support its approval, the Associated Press reported.

"What you're talking about is a potential public health disaster," Graham said of Arcoxia. "We could have a replay of what we had with rofecoxib (Vioxx)."

Another strong critic, Dr. Eric J. Topol, director of the Scripps Translational Science Institute, also found fault with the new drug. Topol first published data on the danger of Vioxx in 2001.

"We don't have the data to know the boundaries of Arcoxia's safety," he said in an interview in April, before the advisory panel's vote. "There is a difference now that there is awareness of heart risk with these drugs. There was not awareness, in fact, there was denial back in 2001."

"If the drug is approved, it would not be the same as what happened years ago," he added. "But I still am concerned that we don't have the cardiovascular safety issue assured. There can be misrepresentation of the drug when it's marketed."

A top Merck official told the advisory panel that the company has "comprehensively characterized the safety and efficacy profile" of Arcoxia.

"We at Merck believe etoricoxib represents a valuable treatment option for patients with osteoarthritis. We would like to emphasize there is more long-term safety data ... for etoricoxib than any other NSAID," said Peter Kim, president of Merck's research laboratories.

But other experts were not convinced.

In prepared testimony for the panel, Dr. Sidney Wolfe, director of the Health Research Group at Public Citizen, said the drug should not be approved in the United States and should be pulled from the market in the more than 60 countries where it is now sold.

"How can the approval of etoricoxib and the large numbers of preventable, life-threatening cardiovascular adverse reactions be justified?" Wolfe said in a prepared statement. "Why should the similarly dangerous offspring of Vioxx be approved? The answer is that it should not."

Wolfe noted that trial data presented by Merck on cardiovascular risks compared etoricoxib with the arthritis pain reliever diclofenac (brand name Voltaren), which he said is much more cardio-toxic than older, safer pain relievers.

"It is time to shut the door on further additions to this dangerous class of cox-2 inhibitor drugs," Wolfe said. "The idea that there may be certain patients, however unidentifiable they are, who might benefit from this drug is just not good enough as a basis for its approval. In addition, further trials on these cox-2 drugs are unethical and should be stopped."

However, as recently as Tuesday, officials at Merck said they would continue to push for Arcoxia's U.S. approval, the AP reported.

Since pulling Vioxx from the market, Merck has faced more than 10,000 lawsuits from former patients and their families.

More information

For more information on heart disease and cox-2 inhibitors, visit the American Heart Association.

SOURCES: April 27, 2007, Associated Press; April 12, 2007, U.S. Food and Drug Administration teleconference with Robert Meyer, M.D., M.P.H., director, Office of Evaluation II, Center for Drug Evaluation and Research; Bob Rappaport, M.D., director, Office of Drug Evaluation II, Division of Anesthesia, Analgesia and Rheumatology Products, and John Jinkins, M.D., director new drugs; Eric J. Topol, M.D., director, Scripps Translational Science Institute, La Jolla, Calif.; April 12, 2007, press statement, Public Citizen