Merck released outcomes data on experimental COX-2 drug Arcoxia, prompting mixed reviews including some from doctors who said the results do not support approval.
Arcoxia (etoricoxib), a cox-2 drug which Merck hopes will replace withdrawn pain killer Vioxx, demonstrated similar rates of confirmed thrombotic cardiovascular (CV) events compared to diclofenac and fewer upper gastrointestinal events, the company said.
Physicians were critical of Arcoxia’s side effects and of the study’s methodology, specifically that Merck chose to test the compound against diclofenac, an older painkiller known to raise heart risks.
“The development program for Arcoxia is fatally flawed,” Dr. Steven Nissen, a Cleveland Clinic cardiologist and former head of the FDA’s cardiac drug advisory panel, told the Associated Press. “My advice to the FDA is that they should not approve this drug.”
Dr. David Graham, the FDA drug safety expert who blew the whistle on his agency’s handling of Vioxx, concurred, saying Merck went with diclofenac to avoid a repeat of what happened with its VIGOR study, which uncovered Vioxx’s cardiovascular risk.
Arcoxia is available in 62 countries. Merck, which recently responded to an “approvable” letter from the FDA on Arcoxia, expects to hear from the FDA in April.
Merck pooled results from three studies including a total of 34,701 patients. After 18 months of testing separate cohorts on each drug, there was no evidence of a difference between the treatment groups for certain thrombotic CV events: Of the 17,412 patients who received Arcoxia, 320 had clot-related heart problems compared to 323 of the 17,289 patients taking diclofenac.
As far as side effects, Arcoxia users were 30% less likely to have ulcers, stomach bleeding or other gastrointestinal problems, but both cohorts showed similar rates of serious problems.
Among those who discontinued treatment, 20% of the discontinuations were due to side effects. More people quit Arcoxia because of high blood pressure; more stopped diclofenac because of stomach or liver problems. Congestive heart failure was rare but more common among those receiving a higher dose of Arcoxia than among those on a lower dose or diclofenac.
The data are being presented today at the American Heart Association 2006 Scientific Sessions, at the American College of Rheumatology 2006 Scientific Meeting and in an online publication in The Lancet.