The second-generation cyclooxygenase (COX) 2 inhibitor etoricoxib (Arcoxia ^R ) has moved a step closer to approval with the announcement by the Food and Drug Administration (FDA) that the drug's manufacturer, Merck & Co, Inc, had received an "approvable letter."

In the October 29 letter, the FDA informed Merck that additional safety and efficacy data are required before the new drug application for etoricoxib could move forward.

Although the second-generation COX-2 inhibitors, such as etoricoxib, are more COX-2-specific, and therefore should be more gastrointestinal (GI) friendly than the first-generation agents, the definitive answers await additional clinical data, according to Roy Fleischmann, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center in Dallas. He added that the recently withdrawn rofecoxib (Vioxx) and celecoxib (Celebrex) differ with respect to their COX-2 specificity but do not appear to differ in terms of their relative GI protection.

However, Dr. Fleischmann, a member of the CIAOMed editorial board, noted that patients and physicians would benefit from the addition of a new nonsteroidal anti-inflammatory agent drug, regardless of whether the drug is more or less COX-2 specific. "The advantage of having a new nonsteroidal is real," he said. "Not all patients respond to all the nonsteroidals that are available. There will always be a group of patients who will respond to a newer drug who had not responded to the older drugs.

A study reported last month at the annual meeting of American College of Rheumatology in San Antonio, Texas, found that in osteoarthritis patients who were randomly assigned to either etoricoxib or diclofenac, the etoricoxib group had a 50% lower discontinuation rate due to gastrointestinal side effects. ¹

Lead researcher Herbert S.B. Baraf, MD, of George Washington University, Washington, DC, also showed that patients treated with etoricoxib or diclofenac had similar rates of thrombotic cardiovascular events, though they acknowledged that more patients in the etoricoxib group discontinued because of increases in blood pressure.

More attention has been focused on cardiovascular events since Merck's first-generation COX-2 inhibitor rofecoxib (Vioxx) was withdrawn from the market after a study showed that the drug doubled the risk of heart attack and stroke compared to placebo when taken for more than 18 months.

In announcing the FDA had issued the approvable letter, Merck did not state what type of additional data would be required to receive final approval for etoricoxib. Merck chairman Raymond V. Gilmartin said the company will work with FDA to address whatever steps need to be taken to secure final approval of etoricoxib's NDA.

The company is seeking approval to market etoricoxib for the treatment of osteoarthritis, rheumatoid arthritis, chronic low back pain, acute pain, menstrual pain, acute gout, and ankylosing spondylitis.

References:

1. Baraf HSB, Fuentealba C, Greenwald M, et al. Tolerability and effectiveness of etoricoxib compared to diclofenac sodium in patients with osteoarthritis: a randomized controlled study (EDGE trial). Presented at: Annual Meeting of the American College of Rheumatology; San Antonio, Texas. Abstract 832.