Merck & Co’s latest foray into the COX-2 arena, Arcoxia (etoricoxib), shows an increases risk of cardiovascular adverse events in “a number of analyses,” according to briefing documents from this week’s US Food and Drug Administration advisory committee review of the class of products.
“A number of analyses… support the conclusion that there is an increase in CV events in [Arcoxia] treated subjects compared to placebo,” the briefing documents state. The materials also suggest “significant” safety questions about the product, which the FDA has been deemed “approvable” [[01/11/04a]]. According to the agency’s website, the FDA also found a cardiovascular safety signal in the Arcoxia arm of a trial comparing the drug with the standard therapy, diclofenac, in osteoarthritis patients – but reviewers noted that the overall rate of cardiovascular thromboembolic side effects was similar between the two products. Arcoxia is also said to have shown a heightened risk for both congestive heart failure-related events and hypertension, with a “marginal” gastrointestinal benefit.
The briefing documents, which track the history of Merck’s now-withdrawn COX-2 Vioxx (rofecoxib) [[01/10/04a]], also include data on Pfizer’s Bextra (valdecoxib) and Celebrex (celecoxib) offerings, and highlight concerns with two other drugs in the class – Novartis’ Prexige (lumiracoxib) and Pfizer’s Dynastat (parecoxib). They claim that Novartis’ 18,000-patient Target study, comparing Prexige to ibuprofen and naproxen, “has not definitively answered the question whether [Prexige] increases cardiovascular thrombotic risk as compared to non-selective [non-steroidal anti-inflammatory drugs].”