INDEPENDENT ANALYST COMMENT

Clare Churchill, Datamonitor Healthcare Analyst

London Friday April 8, 2005- The Food and Drug Administration (FDA) and European Medicines Agency (EMEA) have announced important changes to the currently marketed non-steroidal anti-inflammatory (NSAID) class of drugs. Both have advised the withdrawal of Pfizer’s Bextra (valdecoxib) from the market, but the FDA announcement also affects other members of the NSAID class, including Cox-2s, prescription and over-the-counter (OTC) NSAIDs. The voluntary withdrawal of Merck’s Vioxx (rofecoxib) from the market in September 2004 sparked investigations in both regulatory bodies, and following six months of data review this is the first clear sign of action.

"Today's actions protect and advance the health of the millions of Americans who rely on these drugs everyday," Acting Director of FDA's Centre for Drug Evaluation and Research (CDER) Dr. Steven K. Galson said.

"The FDA is providing the public information based on the latest available scientific data to guide the careful and appropriate use of these drugs aimed at maximizing their potential benefits and minimizing their risks."

The main EMEA action points are:

•           Suspension of Bextra sales in the EU has been requested by the EMEA. Physicians are advised not to initiate any new patients and to closely monitor their current patients. This suspension is an interim measure pending the finalisation of the assessment of Cox-2 inhibitors by the EMEA.

•           The EMEA has made no mention of other Cox-2s currently on the market in the EU, which include Pfizer’s Celebrex (celecoxib) and Dynastat (paracoxib), the pro-drug of Bextra, and Merck’s Arcoxia (etoricoxib).

The major FDA action points are:

•           The FDA has requested the withdrawal of Bextra (valdecoxib) from the market and Pfizer has agreed to suspend marketing in the US . Bextra was the most severely condemned product of the currently marketed Cox-2s at the advisory committee, with the committee vote only recommending that it remain on the market by a two vote margin. The Chairman of the committee, Alastair Wood, strongly campaigned against Bextra in the meeting. The FDA on reviewing this data has agreed that the risk is too high, with no unique benefit offered.

•           Celebrex is to have a black box warning stating the risks in terms of cardiovascular (CV) side-effect. The wording of this will be worked out between the FDA and Pfizer, but is likely to refer to both the risk found in clinical trials, and the apparent class wide effect. This black box may also contain risk information for gastrointestinal (GI) and dermatological side-effects associated with all NSAIDs.

•           Manufacturers of all prescription NSAIDs, including Celebrex, will be asked to include a medication guide for patients in their packaging, with updated label warnings about the CV and GI side-effects. This guide will increase patient awareness of the risks associated with these products, and will discourage their use in less essential indications, where alternatives are readily available.

•           Manufacturers of OTC NSAIDs have also been asked to review their labelling to include more specific information about the potential CV and GI effects, as well as potential skin reactions, which are already included on prescription warning labels.

This action corresponds to advice given by the FDA arthritis advisory committee panel, which convened for a three day discussion in February this year.

(12/4/05)