MERCK RESPONDS TO APPROVABLE LETTERS FOR ARCOXIA

Merck has submitted a response to the FDA's approvable letters for its new drug applications (NDAs) for Arcoxia (etoricoxib). The original NDA was submitted in December 2003, and a separate NDA for a 30-mg dose of Arcoxia was submitted in April 2004. Arcoxia has been under review by the FDA as an investigational selective COX-2 inhibitor since 2003 and is currently available in 62 countries in Europe, Latin America, the Asia-Pacific region and the Middle East.

The response to the approvable letters includes the results of the MEDAL Program, the first arthritis study program to have cardiovascular events as a primary endpoint and the largest and longest arthritis study program ever undertaken, according to the company. These results, published online in The Lancet, show that Arcoxia demonstrated similar rates of confirmed thrombotic cardiovascular events compared with diclofenac, the most widely prescribed non-steroidal anti-inflammatory drug (NSAID).

In the prespecified per-protocol analysis of the primary endpoint, the relative risk of confirmed thrombotic cardiovascular events between Arcoxia and diclofenac was 95 percent. In the MEDAL Program, the confirmed rates of upper gastrointestinal (GI) clinical events, which include perforations, ulcers, bleeding and obstructions, were significantly lower with Arcoxia than with diclofenac. However, there was no significant difference in the rates of confirmed, complicated upper GI clinical events, which include perforations, obstructions and major bleeding, between Arcoxia and diclofenac.

Conducted at 1,380 sites in 46 countries, the MEDAL Program was a prospectively designed clinical program combining thrombotic cardiovascular safety data from three trials: MEDAL, EDGE and EDGE II. The primary objective of the MEDAL Program was to perform a non-inferiority analysis of confirmed thrombotic cardiovascular events following daily treatment of Arcoxia (60 or 90 mg daily) or diclofenac (150 mg daily) in osteoarthritis and rheumatoid arthritis patient populations. The intent of the study was not to assess absolute risk; this would have required a placebo group, which would be unethical in a long-term arthritis study, according to Merck.