December 7, 2010, 4:42 pm
<!– — Updated: 4:14 pm –>
F.D.A. Panel Backs New Diet Pill
By ANDREW POLLACK
12/8/10 | Updated with more detail
A federal advisory committee on Tuesday recommended approval of what could become the first new prescription diet pill in more than a decade.
The advisory committee to the Food and Drug Administration voted 13 to 7 that the benefits of the drug, Contrave, exceeded its risks. The drug was developed by Orexigen Therapeutics of San Diego.
The endorsement is the first positive sign in a long time for pharmaceutical companies trying to develop medicines to treat the nation’s epidemic of obesity.
In recent months, the same advisory committee voted against approval of two other weight-loss drugs — Qnexa from Vivus and lorcaserin from Arena Pharmaceuticals — primarily because of safety issues. Both drugs subsequently were rejected by the F.D.A. itself.
Also, the drug Meridia, from Abbott Laboratories, was taken off the market in October after a study showed it might increase the risk of heart attacks and strokes. That has left only one prescription drug, Roche’s little-used Xenical, which was approved in 1999, for long-term use in losing weight.
The F.D.A. is expected to decide whether to approve Contrave by Jan. 31. It usually, though not always, follows its committees’ advice.
Contrave would be the first marketed product for Orexigen, which was founded in 2002. Takeda Pharmaceutical, the largest Japanese drug company, will market Contrave in the United States, possibly with Orexigen.
With Contrave, the big issue was that the drug had only modest effectiveness while also causing a slight increase in blood pressure and pulse rate. That could conceivably raise the risk of heart attacks and strokes, though the trials conducted by Orexigen were too small and too short to determine that.
Both the F.D.A. and the company said that a larger trial to look specifically at risk of heart attacks and other cardiovascular problems would be conducted. The advisory committee voted 11 to 8, with one abstention, that that study could be done after the drug was approved.
Requiring such a trial before approval “would kill the development” of the drug, said Dr. William R. Hiatt, a committee member who is a professor of cardiovascular research at the University of Colorado. Such a trial is expected to involve at least 10,000 patients and could take years.
But another cardiologist on the committee, Dr. Sanjay Kaul of Cedars-Sinai Medical Center in Los Angeles, said the trial should be done first.
“We need to make sure that we get it right the first time,” Dr. Kaul said. He voted against approval of Contrave, though he said he might have backed it if the drug were more effective in helping people lose weight.
In four clinical trials involving a total of about 4,500 people, those who took Contrave lost an average of 4.2 percentage points of their weight more than those taking a placebo after one year. That fell short of the standard set by the F.D.A. that a drug should produce a weight loss at least 5 percentage points greater than placebo.
However, in most of the trials, Contrave did meet a second F.D.A. requirement that twice as many patients on the drug as on placebo lose at least 5 percent of their weight. Meeting only one of the two standards is enough for approval.
“I think they made it by the hair of their chinny chin chin,” said Melanie G. Coffin, the patient representative on the committee, who voted in favor of approval. “It’s sad to see that that is as far as they could go.”
Contrave is a combination of two existing drugs that, Orexigen says, work together to quell food cravings. One of them, bupropion, is an antidepressant also known by the brand name Wellbutrin that is also sold under the name Zyban to help people quit smoking. The other, naltrexone, is approved to treat alcohol and drug addiction.
Some panel members said that since those drugs had long been used, the safety risks were fairly well understood. One is that bupropion can cause seizures. Dr. Michael A. Rogawski, a neurologist on the committee, said that because of that risk, Contrave should be used only in special circumstances.
A subtext of the meeting was whether the F.D.A. was setting the bar too high for obesity drugs. Several groups that advocate for obese people, or treat them, testified in favor of approval of Contrave. But their arguments were not so much about the drug itself as about the need for more options and about the attitude of the F.D.A.
“This panel has voted against every obesity treatment that has come before it this year,” said Theodore K. Kyle of Pittsburgh, a former industry executive who is in several advocacy groups for the obese. “I ask you to take the disease seriously and take the benefits of treatment seriously.”
Last Friday, a different F.D.A. advisory panel recommended lowering the weight requirement for weight-loss surgery involving Allergan’s stomach-restricting Lap-Band device.
But regarding Contrave, three groups — Public Citizen, the National Research Center for Women and Families and the National Women’s Health Network — urged the panel to vote against approval, saying the risks were too great and its effectiveness in weight loss too small.
People who are obese have a higher risk of death and of various diseases, like diabetes. Some studies have shown that weight loss of even 5 to 10 percent can reduce those risks.
But a concern was that the increase in blood pressure and heart rate caused by Contrave might nullify any health benefits from the weight loss.
This is what happened with Abbott’s Meridia, which was approved in 1997 despite raising blood pressure and pulse rate in clinical trials. When a big cardiovascular study was finally conducted, it found an increased risk of heart attacks and strokes.
Trading in Orexigen’s shares was halted all day. But the panel’s positive vote buoyed the stock of other obesity drug developers, in part because it suggested they would not have to do lengthy heart safety studies before approval.
Shares of Vivus rose nearly 11 percent to close at $7.80, then shot up 13 percent more to $8.82 after hours. Arena shares rose 2 percent to $1.41 in regular trading and then nearly 11 percent more to $1.56 after hours.
A federal advisory committee on Tuesday recommended approval of what could become the first new prescription diet pill in more than a decade.
The advisory committee to the Food and Drug Administration voted 13 to 7 that the benefits of the drug, Contrave, exceeded its risks. The drug was developed by Orexigen Therapeutics of San Diego.
The endorsement is the first positive sign in a long time for pharmaceutical companies trying to develop medicines to treat the nation’s epidemic of obesity.
In recent months, the same advisory committee voted against approval of two other weight-loss drugs — Qnexa from Vivus and lorcaserin from Arena Pharmaceuticals — primarily because of safety issues. Both drugs subsequently were rejected by the F.D.A. itself.
Also, the drug Meridia, from Abbott Laboratories, was taken off the market in October after a study showed it might increase the risk of heart attacks and strokes. That has left only one prescription drug, Roche’s little-used Xenical, which was approved in 1999, for long-term use in losing weight.
The F.D.A. is expected to decide whether to approve Contrave by Jan. 31. It usually, though not always, follows its committees’ advice.
Contrave would be the first marketed product for Orexigen, which was founded in 2002. Takeda Pharmaceutical, the largest Japanese drug company, will market Contrave in the United States, possibly with Orexigen.
With Contrave, the big issue was that the drug had only modest effectiveness while also causing a slight increase in blood pressure and pulse rate. That could conceivably raise the risk of heart attacks and strokes, though the trials conducted by Orexigen were too small and too short to determine that.
Both the F.D.A. and the company said that a larger trial to look specifically at risk of heart attacks and other cardiovascular problems would be conducted. The advisory committee voted 11 to 8, with one abstention, that that study could be done after the drug was approved.
Requiring such a trial before approval “would kill the development” of the drug, said Dr. William R. Hiatt, a committee member who is a professor of cardiovascular research at the University of Colorado. Such a trial is expected to involve at least 10,000 patients and could take years.
But another cardiologist on the committee, Dr. Sanjay Kaul of Cedars-Sinai Medical Center in Los Angeles, said the trial should be done first.
“We need to make sure that we get it right the first time,” Dr. Kaul said. He voted against approval of Contrave, though he said he might have backed it if the drug were more effective in helping people lose weight.
In four clinical trials involving a total of about 4,500 people, those who took Contrave lost an average of 4.2 percentage points of their weight more than those taking a placebo after one year. That fell short of the standard set by the F.D.A. that a drug should produce a weight loss at least 5 percentage points greater than placebo.
However, in most of the trials, Contrave did meet a second F.D.A. requirement that twice as many patients on the drug as on placebo lose at least 5 percent of their weight. Meeting only one of the two standards is enough for approval.
“I think they made it by the hair of their chinny chin chin,” said Melanie G. Coffin, the patient representative on the committee, who voted in favor of approval. “It’s sad to see that that is as far as they could go.”
Contrave is a combination of two existing drugs that, Orexigen says, work together to quell food cravings. One of them, bupropion, is an antidepressant also known by the brand name Wellbutrin that is also sold under the name Zyban to help people quit smoking. The other, naltrexone, is approved to treat alcohol and drug addiction.
Some panel members said that since those drugs had long been used, the safety risks were fairly well understood. One is that bupropion can cause seizures. Dr. Michael A. Rogawski, a neurologist on the committee, said that because of that risk, Contrave should be used only in special circumstances.
A subtext of the meeting was whether the F.D.A. was setting the bar too high for obesity drugs. Several groups that advocate for obese people, or treat them, testified in favor of approval of Contrave. But their arguments were not so much about the drug itself as about the need for more options and about the attitude of the F.D.A.
“This panel has voted against every obesity treatment that has come before it this year,” said Theodore K. Kyle of Pittsburgh, a former industry executive who is in several advocacy groups for the obese. “I ask you to take the disease seriously and take the benefits of treatment seriously.”
Last Friday, a different F.D.A. advisory panel recommended lowering the weight requirement for weight-loss surgery involving Allergan’s stomach-restricting Lap-Band device.
But regarding Contrave, three groups — Public Citizen, the National Research Center for Women and Families and the National Women’s Health Network — urged the panel to vote against approval, saying the risks were too great and its effectiveness in weight loss too small.
People who are obese have a higher risk of death and of various diseases, like diabetes. Some studies have shown that weight loss of even 5 to 10 percent can reduce those risks.
But a concern was that the increase in blood pressure and heart rate caused by Contrave might nullify any health benefits from the weight loss.
This is what happened with Abbott’s Meridia, which was approved in 1997 despite raising blood pressure and pulse rate in clinical trials. When a big cardiovascular study was finally conducted, it found an increased risk of heart attacks and strokes.
Trading in Orexigen’s shares was halted all day. But the panel’s positive vote buoyed the stock of other obesity drug developers, in part because it suggested they would not have to do lengthy heart safety studies before approval.
Shares of Vivus rose nearly 11 percent to close at $7.80, then shot up 13 percent more to $8.82 after hours. Arena shares rose 2 percent to $1.41 in regular trading and then nearly 11 percent more to $1.56 after hours.