Analysis: Merck's COX-2 bid quashed

WASHINGTON, April 12 (UPI) -- A federal advisory panel on Thursday rejected Merck's bid to market a new osteoarthritis medication amid concerns that it may carry cardiovascular risks akin to Vioxx.

The 20-to-1 decision makes it highly unlikely that the Food and Drug Administration will approve the drug, known as Arcoxia.

"We got what appears to be a very clear vote advising us against approval," said Robert Meyer, director of FDA's office of drug evaluation.

Arcoxia is in the class of non-steroidal anti-inflammatory drugs known as COX-2 inhibitors, which includes Vioxx and Bextra. Merck pulled Vioxx from the U.S. market in 2004 because of evidence it increased patients' risk for heart attacks and strokes.

Bextra was also removed, while a third drug, Celebrex, is still selling on a limited basis.

Arcoxia has been sold for the past five years in Europe and in dozens of other countries around the world. The drug represented Merck's first bid to return to the once-lucrative COX-2 pain drug market in the United States.

The company had hoped to convince experts that the drug was a safer and more effective pain reliever than related drugs.

"Patients with osteoarthritis want and deserve additional treatment options," said Scott Korn, Merck's executive director of regulatory affairs.

But experts and some FDA officials criticized Merck for using what they called poorly designed scientific studies in an attempt to put Arcoxia in the best possible light.

Panel member David Felson noted that more than 20 non-steroidal anti-inflammatory drugs (NSAIDs) are already on the U.S. market.

"There is nothing special about this drug that would warrant giving it to patients and putting them at risk of cardiovascular death," said Felson, a professor of medicine at the Boston University School of Medicine.

After hearing Merck's results, Felson said he concluded that "20 is enough".

COX-2 drugs have never been shown to be better pain relievers than older NSAIDs like ibuprofen. But doctors eagerly prescribed them in part because they tend to cause fewer ulcers and less gastrointestinal bleeding.

Robert Shibuya, an FDA medical officer, told experts "there is little doubt" that Arcoxia is an effective pain reliever.

Merck studies showed Arcoxia carries similar cardiovascular risks as an older NSAID called diclofenac. But FDA scientists attacked the study, saying it was inappropriate to use it as a safety benchmark for U.S. patients.

Trials that caused the withdrawal of Vioxx and Bextra compared the drugs' cardiovascular safety to naproxen, an older NSAID. When the same standard was applied to Arcoxia, its cardiovascular risk was found to be 2.7 times higher than naproxen's, agency officials said.

FDA scientist David Graham reported an analysis estimating that every one million patients would cause between 6,800 and 30,000 additional heart attacks each year if they were treated with Arcoxia instead of naproxen.

"What you're talking about is a potential public health disaster," said Graham, who played a key role in publicizing safety problems with other COX-2 drugs in 2004. "And then we'll have a repeat of what we had with (Vioxx)," he said.

Sean Curtis, Merck's director of clinical research, acknowledged safety concerns surrounding COX-2 drugs. He said the company would refrain from direct-to-consumer advertising until doctors were educated about Arcoxia's cardiovascular risks and its gastrointestinal benefits.

"One has to make these tradeoffs on a reasonable patient basis," he said.

But the assurances failed to convince panelists.

"The idea should not be that we need new drugs. The idea should be that we need better drugs," said Martha Solanche, a consumer representative on the panel.

Merck spokeswoman Kyra Lindeman said following the vote that the company was "disappointed" in the result. "We continue to believe Arcoxia has the potential to become a valuable treatment option for patients suffering from osteoarthritis," she said.