F.D.A. Panel Votes Against Obesity Drug
By ANDREW POLLACK
Published: July 15, 2010 From the NY Times
A federal advisory committee voted narrowly against endorsing a drug vying to become the first new prescription medicine for obesity in more than a decade, signaling heightened concerns for possible health risks associated with a new generation of diet pills.
The advisory committee to the Food and Drug Administration voted 10 to 6 that the safety concerns, like increased heart rate, possible birth defects and psychiatric problems, overrode the potential benefits of the drug, called Qnexa and developed by Vivus.
The meeting was closely watched by both the medical community and Wall Street as a sign of how the F.D.A. might handle new obesity drugs. Typically, the agency has paid extraordinary attention to safety because weight-loss drugs have a history of safety problems and because the medicines are likely to be used by millions of people for long periods of time.
The committee vote suggests that drug safety will continue to be paramount.
“No one wants to conduct a large public health experiment on the population,” one panel member, Elaine H. Morrato of the University of Colorado, Denver, said.
The F.D.A. is scheduled to decide by late October whether to approve Qnexa. It usually abides by the advice of its advisory committees. But a split vote like this one is often viewed by the agency as less definitive. Indeed, several panel members said they could just as easily have voted the other way.
The outcome of the meeting could portend a more difficult time for two other new obesity drugs that will face advisory committee hearings this year — lorcaserin from Arena Pharmaceuticals and Contrave from Orexigen Therapeutics.
The F.D.A. and most panel members did not question the effectiveness of Qnexa. Results from clinical trials suggested that in reducing weight, Qnexa was superior to the currently approved drugs and to the other two possible new ones.
Those getting the highest dose of Qnexa lost an average of 10.6 percent of their weight after one year, compared to 1.7 percent for those on a placebo.
The F.D.A. had five safety concerns that the panel spent most of the day addressing: possible psychiatric problems like depression and suicidal thinking, impaired memory and concentration, acid buildup in bodily fluids that could increase the risk of kidney stones, an increase in heart rate that could portend cardiac problems and possible birth defects.
Qnexa is a combination of two already approved drugs: phentermine, the part of the fen-phen combination that remained on the market after fen-phen was withdrawn in 1997 for causing heart valve problems, and topiramate, an epilepsy and migraine drug sold as Topamax by Johnson & Johnson. Phentermine, a stimulant, is responsible for the faster heartbeat, and topiramate causes the other side effects.
Leland F. Wilson, the chief executive of Vivus, said the company was disappointed with the vote but not deterred from trying to win approval. “The advisory committee vote is a recommendation, not a final step,” he said in a brief conference call.
Trading in Vivus, based in Mountain View, Calif., was halted on Thursday during the panel’s meeting, but shares plummeted 56 percent, to $5.27, in early after-hours trading. Shares of both Orexigen and Arena fell late in the day after the committee vote.
In after-hours trading, however, Arena was up somewhat. That could be because investors see its drug as having a better safety profile than Qnexa, although it is less effective in reducing weight.
About one-third of American adults are obese and another third overweight, so a successful diet drug could garner sales of billions of dollars a year.
Yet there have been few, if any, successful obesity drugs. The two existing drugs approved for long-term use — Meridia from Abbott Laboratories and Xenical from Roche — have modest sales, in part because of side effects and limited efficacy. Three years ago, the F.D.A. declined to approve rimonabant from Sanofi-Aventis because of concerns about suicide risk and depression.
Vivus argued on Thursday that obesity itself was a health risk, associated with a higher risk of diabetes, heart disease and other problems. “Obesity treatment can improve health and save health care dollars,” Dr. Louis J. Aronne, an obesity expert at Weill Cornell Medical College and a consultant to Vivus, told the committee. “Weight loss now appears to be like a gift that keeps on giving.”
In the trial, Qnexa improved blood pressure, blood sugar and cholesterol levels. But Dr. Mary Roberts, the F.D.A. reviewer of the drug, said it was unclear if the improvements would translate into what really matters, a reduction in heart attacks, strokes and death.
Bariatric surgery, which can produce weight loss of 15 percent or more, has been shown to reduce risk of heart attacks and prolong lives. But the only study that tested this for a diet drug — Meridia — actually found an increase in heart attack risk.
Most of the committee members spent two days this week on another panel weighing whether the diabetes drug Avandia should be removed from the market because of suggestions it raises the risk of heart attack.
That seemed to color the debate on Qnexa a little. Some committee members said that the yearlong trials of Qnexa did not provide enough information to judge long-term risks and that it was better to keep the drug off the market than to have problems arise later.