F.D.A. Panel Urges Denial of Diet Drug

F.D.A. Panel Urges Denial of Diet Drug
By ANDREW POLLACK
Copyright by The New York Times
Published: September 16, 2010
http://www.nytimes.com/2010/09/17/health/17drug.html?hpw


A federal advisory panel on Thursday recommended against approval of a new diet pill, the latest setback in efforts to develop treatments for the nation’s obesity epidemic.

The advisers to the Food and Drug Administration voted 9 to 5 that the potential benefits of the drug, called lorcaserin and developed by Arena Pharmaceuticals, did not outweigh the risks.

The vote indicated how tough it might be to win approval for obesity drugs. Some committee members said lorcaserin was not clearly unsafe. But even a mere suggestion of possible risks seemed unacceptable to some panel advisers because the drug did not help people lose much weight.

“I really didn’t have a lot of issues with the risk,” said one panel member, Dr. Eric I. Felner, a diabetes expert at Emory University. Still, he voted no. “I just didn’t see it as being that efficacious.”

The negative vote is the second setback this year in attempts to win approval for what would be the first new prescription weight-loss drug in more than a decade.

Citing safety concerns, the same committee voted 10 to 6 in July against approval for the drug Qnexa from Vivus, a drug that produced a much greater weight loss among trial participants than lorcaserin.

The F.D.A., which usually takes the advice of its committees, is expected to decide next month whether to approve lorcaserin or Qnexa.

On Wednesday, the advisory panel split 8 to 8 on whether the diet drug Meridia, sold by Abbott Laboratories, should be removed from the market. A study showed that it increased the risk of heart attacks and strokes in patients with cardiovascular risk. The drug has already been removed from the market in Europe.

Some doctors who treat obesity testified in favor of the drug at Thursday’s meeting, which was held in Adelphi, Md. They said there was an urgent need for new diet drugs, given that a third of American adults are obese and another third overweight. There is hope that drugs that help people lose weight would also mitigate some of the health problems linked to obesity, like diabetes, heart disease and cancer.

Yet the F.D.A. has become safety-conscious in this area since the drugs could potentially be taken for years by millions of people, and because of highly publicized health concerns associated with some previously popular diet prescriptions, like Meridia and the so-called fen-phen combination that damaged heart valves.

Lorcaserin mimics the effect of the brain chemical serotonin and has an effect on suppressing appetite. Its mechanism of action is similar to that of fenfluramine, the part of the fen-phen regimen that was pulled from the market.

Arena, which is based in San Diego, said its drug was developed to work in the brain and not the heart. In its clinical trials, those who took the drug did not have a significantly higher rate of valve problems than those who got a placebo. The F.D.A. said, however, that statistically the company could not totally rule out an increased risk of up to 50 percent.

The biggest safety issue for the committee seemed to be the finding of tumors in rats that had received high doses of the drug. Arena argued that those findings would not apply to people. In the clinical trials, there was no increase in cancer rates among people who took the drug.

For the committee, even though the safety issues were not considered so bad, they were measured against an efficacy that was not too good. The drug met only one of the two F.D.A. standards for weight loss drugs, and it did so only by what the F.D.A. termed a “slim margin.”

Those taking the drug lost 5.8 percent of their weight after a year, compared to 2.5 percent for those getting a placebo. The difference, 3.3 percentage points, is below the 5 percentage point criterion set by the F.D.A.

However, 47 percent of those taking lorcaserin lost at least 5 percent of their weight, compared to 22 percent of those getting a placebo. That just exceeded the F.D.A. standard that twice as many people on the drug as on the placebo lose 5 percent of their weight.

Those who took the drug in the trial had modest improvements in risk measures like blood pressure, cholesterol and blood sugar compared with those who got the placebo, but the significance seemed unclear to the committee.

“The argument that there is an urgent need I don’t think really mitigates the concern of putting a drug that doesn’t do much and may do harm on the market,” said Dr. Pamela S. Douglas, professor of research in cardiovascular diseases at Duke and a committee member.

No patients who used the drug in clinical trials testified to the committee for its approval. And some advocacy groups for women or overweight people said the drug was not ready for approval.

Jack Lief, the chief executive of Arena, said in a statement after the meeting that the company believed that lorcaserin “has a positive benefit-risk profile.” If approved, lorcaserin would be Arena’s first product, and it would be marketed by part of the Japanese drug company Eisai.

Trading in Arena’s stock was halted on Thursday. But after hours, the stock price fell about 40 percent.

But shares of Orexigen Therapeutics, which has a diet pill that will be discussed by the committee in December, rose 38 percent. Investors apparently believe that Orexigen now has the best shot of approval. Of course, after Vivus’s drug was rejected by the advisory committee in July, it was Arena’s shares that rose sharply as investors bet that it had the best shot.