FDA will require additional long-term clinical data for COX-2 inhibitors following Merck's withdrawal of Vioxx due to increased cardiovascular risk.

Merck announced Sept. 30 that it would withdraw Vioxx (rofecoxib) after data from the APPROVEe trial showed an increased risk of myocardial infarction and stroke after 18 months of treatment (see ¹ [A#14040930002]).

Especially when taken chronically, all non-steroidal anti-inflammatory drugs, including COX-2s, "have cardiovascular effects such as fluid retention and increases in blood pressure," FDA Center for Drug Evaluation & Research Acting Director Steven Galson, MD, said during a same-day media call.

"However, Vioxx is the only one of the approved COX-2 selective agents that has an association with heart attacks and stroke…but all of them do have the connection to increased blood pressure," Galson said.

"I think it's impossible to predict with any surety about what implications this is going to have," he said. "We are concerned about this, and we're going to be more interested in looking at long-term data of the new products that come down the pike."

Merck's Vioxx follow-on compound, Arcoxia (etoricoxib), is under review at FDA, with a user fee date of Oct. 30.

Novartis expects to submit an NDA for its COX-2 Prexige (lumiracoxib) by 2006 (² Also see "Prexige TARGET Study: Not Quite A Bull's-Eye For Novartis" - Pink Sheet, 19 August, 2004.).

Galson indicated that FDA would also seek long-term data for COX-2 drugs already on the market. Currently marketed COX-2s include Pfizer's Celebrex (celecoxib) and Bextra (valdecoxib).

"It's really premature for us to say right now how our requirements are going to change," Galson said. "I'm sure that we're going to ask for more long-term data, but I can't tell you exactly what that data is."

Merck met with FDA on Sept. 28 to advise the agency about the results of the APPROVe study and of the company's decision to voluntarily withdraw Vioxx from the market.

FDA said Merck is initiating a market withdrawal "at the pharmacy level."

"We think Merck is doing the right thing here by withdrawing Vioxx, although the risk that an individual patient would have a heart attack or stroke related to this drug is small," Galson said.

FDA said it did not discuss with Merck potential alternatives - such as creating a MedGuide or adding a boxed warning to labeling - to pulling Vioxx off the market.

The agency issued a public health advisory to notify patients that Vioxx was being withdrawn and said patients should contact their physician for guidance on discontinuation and alternative therapies.

- Tericke Blanchard

FDA Will Require Additional Long-Term Data For COX-2 Inhibitors

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