GI DATA ON MERCK'S ARCOXIA PUBLISHED IN THE LANCET

The results from a prespecified upper gastrointestinal safety analysis of the MEDAL trial comparing Merck's investigational selective Cox-2 inhibitor Arcoxia (etoricoxib) with diclofenac, the most widely prescribed non-steroidal anti-inflammatory drug (NSAID), were published in the Feb. 10 issue of The Lancet, Merck announced.

The results showed that overall upper gastrointestinal (GI) events (bleeding, perforation, obstruction or ulcer) were significantly less common with Arcoxia than with diclofenac in a broad patient population. These results were maintained in patients taking proton pump inhibitors (PPIs) for GI protection and in patients taking low-dose aspirin regularly for cardiovascular protection. However, there was no significant difference in the rates of complicated upper GI events (perforations, obstructions and significant bleeding) for Arcoxia and diclofenac.

"The significant difference in overall upper GI clinical events demonstrated between etoricoxib and diclofenac was driven by uncomplicated symptomatic ulcers, which, although not life-threatening, have clinical impact because they require further medical follow-up and therapy," Loren Laine, the trial's steering committee co-chair, said, adding that the difference in the results between complicated and uncomplicated events could potentially relate to diclofenac's lack of antiplatelet effect.

In the trial, which took place in 46 countries, arthritis patients who had GI risk factors were encouraged to use PPIs and those with cardiovascular risk factors were encouraged to use low-dose aspirin to simulate real-world practice. The trial provides the first comparison of a selective Cox-2 inhibitor and a traditional NSAID to assess the effect of concomitant GI co-therapy with PPIs on long-term risk of upper GI clinical events and upper GI symptoms, and is the largest comparison of these agents in low-dose aspirin users, according to Merck.

Merck submitted a new drug application for Arcoxia in 2003 and, after responding to approvable letters, expects a decision from the FDA toward the end of April. The drug is currently available in 62 countries in Europe, Latin America, Asia and the Middle East.