FDA Advisory Panel to Evaluate Arcoxia - Vioxx Replacement

Patient Expert

On Thursday, April 12 an FDA advisory panel will discuss whether or not to recommend that the FDA approve Merck & Co's COX-2 inhibitor, Arcoxia (etoricoxib).   The drug is manufactured by Merck, the same company that made Vioxx, which was pulled from the market in the fall of 2004.   Merck applied for approval to sell Arcoxia as a treatment for the signs and symptoms of osteoarthritis.

Currently, the only COX-2 inhibitor remaining on the market is Celebrex, made by Pfizer, Inc.   These COX-2 inhibitors are all types of NSAIDs.   Over the counter types of NSAIDs include naproxen (sold as Aleve) and ibuprofen.   The difference between the prescription COX-2s and the OTC NSAIDS (and the big selling point) is that the COX-2s have a lower risk of bleeding ulcers and other GI complications than other NSAIDs.   However, studies have shown that the COX-2s have a higher risk of heart attack and strokes.   Vioxx and Bextra were both subsequently pulled from the market.   Pfizer kept selling Celebrex, but stopped all direct to consumer advertising in late 2004, early 2005.   Pfizer has only begun advertising Celebrex again this month.

According to documents released this week by the FDA, the advisory panel will be focusing specifically on the cardiovascular risks of this drug (and all other drugs from this class) when it evaluates Merck's application.   Any NSAID will merit approval only if it fills an unmet need for a particular group of patients and no other relatively safer alternatives are available to them.

Although Arcoxia is currently sold in 63 other countries, there has been a lot of criticism over the last year of the drug and of the way that Merck designed the drug trials that it uses as evidence in its FDA application.   Merck compared Arcoxia to an older NSAID called diclofenac, finding that the two drugs had similar rates of cardiovascular events.   Diclofenac is not commonly used in the U.S. anymore, but is commonly used in many other countries.   Research published last fall found that diclofenac may carry similar heart attack risk as the lower dosage of Vioxx.

Critics of Arcoxia say that the Arcoxia/ diclofenac comparison is flawed because the latter is a weaker drug.   They say a better comparison would have been to other NSAIDs like naproxen.   Studies of naproxen have not shown an increased cardiovascular risk.   Merck did compare Vioxx to naproxen and found that people taking Vioxx were 5 times as likely to have heart attacks as those taking naproxen.   Several smaller studies, not performed by Merck, have compared Arcoxia to naproxen and found a greater risk of heart attack and strokes in people taking Arcoxia than naproxen, but less than other NSAIDs.   Critics contend that not only should the FDA not approve Arcoxia in the U.S., but it should be pulled from all other countries where it is sold.

I will be watching for the FDA advisory panel to make its recommendation on Thursday.   It should be noted that advisory panel recommendations are non-binding.   I am not sure how often the FDA follows the advisory panel recommendations.