The panel voted unanimously today that there is indeed a clear cardiovascular (CV) risk signal associated with rofecoxib. Although the FDA is not obligated to follow the recommendations of its advisory panels, the agency has previously stated its intention to act quickly on the panel's ruling.
Merck voluntarily withdrew Vioxx from the market on September 30, 2004, after the Adenomatous Polyp Prevention on Vioxx (APPROVe) study was halted due to evidence for an increased risk in heart attack and stroke among patients taking the drug for 18 months or longer. According to a statement issued by Merck Thursday evening, the decision may lead the company to pursue a reintroduction of rofecoxib. "If the advisory committee and the FDA conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers."
Dose restriction is key
Some panel members clearly still had reservations about the reintroduction of rofecoxib. "If we do bring it back, 12.5 mg/day is the only dose that I am comfortable with," Steven Nissen, MD, vice-chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation in Ohio, told the panel. Robust CV signals have been seen at 25 and 50 mg doses.
Allan Gibofsky, MD, JD, professor of medicine and public health at Weill Medical College of Cornell University and attending rheumatologist at the Hospital for Special Surgery and New York Presbyterian Hospital in New York City, called for "restricting the dose to not above 12.5 mg/day, a very strong black box warning, and language making this a less preferable agent whether second or third line."
JRA and compassionate use suggested for rofecoxib
Richard O. Cannon III, MD, clinical director of the division of intramural research at the National Institutes of Health in Bethesda, Maryland, suggested that rofecoxib be used only short-term in adults and long-term only in children with juvenile rheumatoid arthritis (JRA).
Several studies have demonstrated that rofecoxib is effective in relieving the signs and symptoms of JRA in children and adolescents ages 2 to 17. Others on the panel suggested restriction to compassionate use only.
"I would have a very restricted access program, and in children, I think we should be careful to assume that children are not at risk," said meeting chair Alistair J.J. Wood, MD, a professor of medicine and pharmacology at Vanderbilt University Medical Center in Nashville, Tennessee.
Reference:
US Food and Drug Administration. Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee; February 16-18, 2005; Gaithersburg, Md.