COX-2 Inhibitor Debate Rumbles On As Merck Accused Of Delay

A new study suggests that there are important differences between Merck & Co's Vioxx (rofecoxib) and other COX-2 inhibitors and that this may account for variations in cardiovascular safety within this drug class, writes Phil Taylor. The US drug major recently withdrew its blockbuster Vioxx, after an increase in cardiovascular events was observed following 18 months of continuous use of the drug, and this prompted considerable debate about the safety of the overall COX-2 inhibitor class. The new study, published in Atherosclerosis, says Vioxx is not typical of other COX-2 inhibitor drugs. The company with the most to lose if the ‘class effect’ theory is sustained is Pfizer, which sells Celebrex (celecoxib), the first COX-2 inhibitor to reach the market, and follow-up Bextra (valdecoxib). Pfizer was forced to defend its drug last week when a Canadian newspaper published an article linking 14 deaths to Celebrex. Sales of Celebrex and Bextra were $779 million (€601m) and $324 million, respectively, in the third quarter of this year. Over the course of their two-year investigation, the authors of the Atherosclerosis study discovered that Vioxx made certain lipid components of the blood, particularly low-density lipoprotein or "bad" cholesterol, more susceptible to free radical damage - changes that contribute to heart disease. "Vioxx interacts at the molecular level in a way that Celebrex and other non-steroidal anti-inflammatories do not," said lead author Preston Mason, president and founder of Elucida Research, which conducted the study. The group received no drug company funding for the research, but counts Pfizer as a sponsor. In addition to Vioxx and Celebrex the researchers examined two other COX-2 inhibitors, Bextra and Merck's Arcoxia (etoricoxib), which is approved for sale in Europe but had its application withdrawn in the US. They also included a non-selective nonsteroidal anti-inflammatory drugs (NSAIDs - naproxen, diclofenac and ibuprofen) and Boehringer Ingelheim/Abbott Laboratories' Mobic (meloxicam), which also claims COX-2 selectivity. Crucially, they concluded that the effects were independent of Vioxx' COX-2 function, and were not seen with the other drugs.