Pfizer will work with FDA to design a long-term safety study for Celebrex following the agency's decision to recommend a "black box" warning on the COX-2 inhibitor's increased risk for cardiovascular events.

FDA is asking all manufacturers of non-steroidal anti-inflammatory drugs to review the available data on their products, but is specifically asking Pfizer to conduct an additional safety study on celecoxib.

"What we're asking all the manufacturers to do is to go back and re-review all of their existing data from controlled clinical trials to collate that, look at it across studies in a combined fashion and submit that for FDA review," Office of New Drugs Director John Jenkins said during an April 7 media conference call.

"We have asked Pfizer to make a post-marketing commitment to us in writing to conduct a long-term safety trial to further evaluate Celebrex."

FDA's decision follows the recommendations of its Arthritis Drugs/Drug Safety & Risk Management Advisory Committees, which overwhelming voted to keep Celebrex on the market, but with stronger labeling and additional safety studies (¹ Also see "Pfizer Celebrex Continued Marketing Supported By FDA Cmte." - Pink Sheet, 18 February, 2005.).

FDA is taking a harder line on Pfizer's Bextra (valdecoxib), and is asking the company to remove the drug from the market due, in part, to a "special risk" of serious skin infections (see ² Also see "Bextra Pulled From Market, But Pfizer Hopes To Explore Other Options" - Pink Sheet, 7 April, 2005. ).

FDA said it is asking Pfizer - and not manufacturers of NSAIDs - to conduct additional studies because of the "conflicting" safety data on celecoxib to date.

"With Celebrex, there are several studies available currently that have given somewhat conflicting results," Jenkins said. "We think it's very important to do a well-designed study to really try to nail down the question about whether Celebrex itself has a unique risk."

"We have data from several large placebo-controlled trials of Celebrex. Some don't seem to show a risk, others seem to show the risk, and that's particularly why we want to try to nail down the question on Celebrex."

Pfizer discussed its intention to conduct a long-term safety study during an April 5 meeting with analysts.

"We are committed to conducting longer-term comparative benefit and risk studies," Global Human Health President Karen Katen said. "We look forward to...moving ahead with important clinical plans to study the longer-term comparative benefit/risk profile" (³ Also see "Celebrex, Bextra Stabilizing After FDA Advisory Committee Review, Pfizer Says" - Pink Sheet, 5 April, 2005.).

FDA is specifically asking Pfizer to conduct a comparison of Celebrex versus naproxen (Roche's Naprosyn and generics). Naproxen is thought to be cardioprotective.

FDA is also hoping to gather additional data from the public sector.

"We plan to work with the manufacturers and other stakeholders such as the NIH to try to get additional data developed so that can more clearly define...whether there are differences among the individual agents in the class," Jenkins said.

Until then, FDA is considering the cardiovascular risk a class effect, and is requiring a black box warning in labeling for COX-2 inhibitors and older prescription NSAIDs. Over-the-counter NSAIDs will need to include additional safety information on packaging.

- Kate Rawson

Celebrex Long-Term Safety Study Planned

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