Another coxib for arthritis? FDA panel says no

Washington -- A federal advisory committee determined that the cardiovascular risks were too great and the benefits too small for the Food and Drug Administration to approve a new pain medication in the "coxib" subset of nonsteroidal anti-inflammatory drugs, or NSAIDS.

On April 12, the FDA's Arthritis Advisory Committee voted 20-1 against recommending that Arcoxia (etoricoxib) be approved by the agency to treat U.S. patients with arthritis. The drug is available in 63 other countries.

"Clearly one of the things we heard come out of their discussion was that the committee had an overall concern about the cardiovascular safety of this drug," said Robert Meyer, MD, MPH, director of the FDA's Office of Drug Evaluation II of the Center for Drug Evaluation and Research.

The worry seemed to spill over to all the coxibs and possibly NSAIDS in general, with the possible exception of naproxen, Dr. Meyer said.

This feeling is not new. Coxibs had long been under a cloud. Two of the three drugs in that group -- Vioxx (rofecoxib) and Bextra (valdecoxib) -- were withdrawn from the market in 2004 and 2005 respectively because they posed increased cardiovascular risks.

The only coxib still on the market is the prescription drug Celebrex (celecoxib), and it carries warnings of heightened heart risks.

With as many as one in five U.S. adults having been told by their physicians that they have arthritis, according to the Centers for Disease Control and Prevention, the need for effective and safe pain medication is great. Physicians are advising a range of strategies -- including physical activity, weight loss and the judicious use of NSAIDS -- to meet that need.

But etoricoxib is not likely to be included among the available choices. "I feel like we got clear advice from the committee both in the discussion and the vote," Dr. Meyer said.

Although the FDA doesn't have to accept the recommendations of its advisers, it generally does.

"We are disappointed in today's outcome," said Peter Kim, PhD, president of Merck Research Laboratories, which developed Arcoxia. "We continue to believe that Arcoxia has the potential to become a valuable treatment option for many Americans suffering from osteoarthritis."

Another message the FDA's Dr. Meyer said he picked up from the committee's discussion was that companies seeking approval for future NSAIDS, including coxib agents, could expect to find a similarly high bar. It's not enough to have another product on the market with the same level of risk and no unique benefit, he said.

"With 20 drugs available to treat arthritic pain, adding another drug when there are questions about safety didn't make any sense," said Steven Nissen, MD, chair of the Dept. of Cardiovascular Medicine at the Cleveland Clinic in Ohio.

"I think the advisory committee got this right," said Dr. Nissen, who did not serve on the arthritis advisory panel but has been a member of other committees.

Since the panel's recommendation didn't shed any new light on safe and effective treatments for arthritis pain, Dr. Nissen is holding out hope that a trial he is leading might do just that. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen, also called the PRECISION trial, will, "with a little bit of luck," start to report findings in 2010, he said.

The trial is still recruiting 20,000 patients with both heart disease and arthritis and is intended to provide a comparison of the relative cardiovascular risks of celecoxib, naproxen and ibuprofen.

"This is the first large truly independent trial that asks these questions, and we will get a very robust answer," Dr. Nissen predicted.

The three drugs being compared all are believed to have different attributes, although naproxen is generally thought to cause the fewest cardiovascular or gastrointestinal problems, he added.

The trial is very unusual in that it is being funded by Celebrex manufacturer Pfizer but run by the Cleveland Clinic. Everyone involved has agreed not to accept any payment from any manufacturer of the drugs, Dr. Nissen said.

Pfizer is taking a risk with this trial, he said. "But they believe in their drug. They believe it is not different from other NSAIDS. We will find out and call it as we see it."