said Friday it expects the Food and Drug Administration to rule by April on its arthritis drug Arcoxia, a cousin of Vioxx, the painkiller that's no longer on the market.
The company has filed responses to questions the FDA had about Arcoxia and said it plans to announce on Monday the results from a clinical trial that uses cardiovascular safety as its primary goal. Merck says the study, whose acronym is MEDAL, is the first clinical trial of an arthritis drug in which heart safety is the key measuring point.
Merck pulled Vioxx from the market in September 2004 after a company-sponsored trial showed patients who took it for more than 18 months had a higher risk of developing heart problems than patients who took a placebo. The company says there was no statistically significant difference in risk among patients who took the drug for less than 18 months, although critics have questioned Merck's interpretation of the results.
Vioxx and Arcoxia both belong to a drug class known as COX-2 inhibitors. The only COX-2 available in the U.S. is
Celebrex. Arcoxia is available in 62 foreign markets. Merck will submit the MEDAL results to regulators in countries were the drug is already sold as well as to authorities in markets where it's seeking approval for Arcoxia.
Merck asked the FDA to approve Arcoxia in December 2003. The FDA granted conditional approval in October 2004, a few weeks after Vioxx was withdrawn, but said it wanted more data on the drug's safety and effectiveness. That's what Merck will try to show with the results of MEDAL, which started in 2002 and involves more than 34,000 patients.
In August, Merck issued some preliminary results for MEDAL, which compares Arcoxia with an older pain reliever called diclofenac, a drug that's been available in the U.S. since 1988 and is sold under the brand name Voltaren by
Diclofenac, which is now generic, is a nonsteroidal anti-inflammatory drug, the same type of medication as pain relievers like naproxen and ibuprofen. Merck says diclofenac is the most-prescribed NSAID in the world.
Preliminary results showed the rate of blood clots leading to cardiovascular problems for Arcoxia patients was similar to that of diclofenac patients. However, there was a "significantly higher" rate of Arcoxia patients quitting the study because of high blood pressure.
In the tests, some Arcoxia patients received 60 milligrams of the drug while others received 90 milligrams. The stronger dose produced a "significantly higher" drop-out rate vs. diclofenac patients because of edema, a build-up of fluid in the body.
Patients taking the higher dose of Arcoxia were more likely to have congestive heart failure than did diclofenac patients, but diclofenac patients were much more likely to quit because of gastrointestinal and liver problems.
Merck said it has narrowed the scope of its Arcoxia application with the FDA and is seeking approval only for the treatment of osteoarthritis, a degeneration of the joints. MEDAL also tested patients with rheumatoid arthritis, an inflammatory disease.
The company plans to ask for clearance for doses of 30 milligrams and 60 milligrams once-daily. Merck "is continuing its efforts with respect to other doses and indications to support subsequent U.S.
applications," the company said.