By ANDREW POLLACK
A new diet pill from Orexigen Therapeutics narrowly meets the requirements for effectiveness but poses potential cardiovascular risks, reviewers from the Food and Drug Administration said Friday
The agency’s review of the drug was posted on the F.D.A. Web site in advance of a meeting Tuesday in which an advisory committee will be asked whether the drug, known as Contrave, should be approved as a treatment for obesity.
Contrave is the last of a trio of new weight-loss drugs to come before the F.D.A. this year. The first two, Qnexa from Vivus and lorcaserin from Arena Pharmaceuticals, failed to win committee endorsements, and were subsequently not approved by the F.D.A. In both cases, safety concerns were the major issues.
Now the question is whether the third time will be the charm, or whether it will be three strikes, you’re out.
In its review the F.D.A. said that patients treated with Contrave in clinical trials lost 4.2 percentage points more of their weight than those getting the placebo after a year. That falls short of the standard that a drug should produce at least 5 percentage points more of weight loss than a placebo.
But Contrave generally met a second standard — that about twice as many patients on the drug as on placebo lose at least 5 percent of their weight. Meeting one of the two criteria is enough for approval under F.D.A. guidelines.
The major safety concern was that patients who took Contrave had a small but statistically significant increase in blood pressure and heart rate.
The drug “attenuates or eliminates the blood pressure and pulse reduction that are normally seen with weight loss,’’ the F.D.A. reviewers wrote. “It is not known how these vital sign changes in the overweight and obese population would impact cardiovascular risk over the long term.’’
Orexigen’s trials were too short and small to evaluate long-term cardiovascular risks, and only 1 percent of the participants had a history of heart disease, heart attack or stroke.
The F.D.A. said a dedicated study would be needed to determine if the drug raises the risk of heart attacks and strokes. It will ask the advisory committee to vote on whether such a study should be conducted, and if so whether it should be done before the drug is approved – which would delay approval for years — or if it could be done afterward.
The situation is somewhat reminiscent of the obesity drug Meridia, approved in 1997, which also caused a small increase in blood pressure and heart rate.
A large cardiovascular safety study eventually found that the drug did increase the risk of heart attacks and strokes. Under pressure from the F.D.A., Abbott Laboratories removed the drug from the market in October.
“We believe a key goal for Orexigen at the panel will be to convince the members that a controlled trial in CV risk need only be conducted post-marketing,’’ Phil Nadeau, an analyst at Cowen & Company, wrote in a note Friday morning. He added that “the hint of Meridia-like CV effects and near-complete absence of safety data in high CV risk patients will weigh heavily in the assessment of Contrave risk-benefit.’’
But Mr. Nadeau and some other analysts said the F.D.A. review was about as expected and was even in its tone, not leaning toward approval or against it. At noon, Orexigen shares were trading at $4.99, down about 9 percent.
Contrave is a combination of two existing drugs that help quell food cravings. One of them, bupropion, is an anti-depressant 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 side effects of the two component drugs – particularly the risk of seizures from bupropion – were also of concern to the F.D.A. reviewers of Contrave.
http://prescriptions.blogs.nytimes.com/2010/12/03/f-d-a-diet-pill-works-but-has-risks/?ref=health
The agency’s review of the drug was posted on the F.D.A. Web site in advance of a meeting Tuesday in which an advisory committee will be asked whether the drug, known as Contrave, should be approved as a treatment for obesity.
Contrave is the last of a trio of new weight-loss drugs to come before the F.D.A. this year. The first two, Qnexa from Vivus and lorcaserin from Arena Pharmaceuticals, failed to win committee endorsements, and were subsequently not approved by the F.D.A. In both cases, safety concerns were the major issues.
Now the question is whether the third time will be the charm, or whether it will be three strikes, you’re out.
In its review the F.D.A. said that patients treated with Contrave in clinical trials lost 4.2 percentage points more of their weight than those getting the placebo after a year. That falls short of the standard that a drug should produce at least 5 percentage points more of weight loss than a placebo.
But Contrave generally met a second standard — that about twice as many patients on the drug as on placebo lose at least 5 percent of their weight. Meeting one of the two criteria is enough for approval under F.D.A. guidelines.
The major safety concern was that patients who took Contrave had a small but statistically significant increase in blood pressure and heart rate.
The drug “attenuates or eliminates the blood pressure and pulse reduction that are normally seen with weight loss,’’ the F.D.A. reviewers wrote. “It is not known how these vital sign changes in the overweight and obese population would impact cardiovascular risk over the long term.’’
Orexigen’s trials were too short and small to evaluate long-term cardiovascular risks, and only 1 percent of the participants had a history of heart disease, heart attack or stroke.
The F.D.A. said a dedicated study would be needed to determine if the drug raises the risk of heart attacks and strokes. It will ask the advisory committee to vote on whether such a study should be conducted, and if so whether it should be done before the drug is approved – which would delay approval for years — or if it could be done afterward.
The situation is somewhat reminiscent of the obesity drug Meridia, approved in 1997, which also caused a small increase in blood pressure and heart rate.
A large cardiovascular safety study eventually found that the drug did increase the risk of heart attacks and strokes. Under pressure from the F.D.A., Abbott Laboratories removed the drug from the market in October.
“We believe a key goal for Orexigen at the panel will be to convince the members that a controlled trial in CV risk need only be conducted post-marketing,’’ Phil Nadeau, an analyst at Cowen & Company, wrote in a note Friday morning. He added that “the hint of Meridia-like CV effects and near-complete absence of safety data in high CV risk patients will weigh heavily in the assessment of Contrave risk-benefit.’’
But Mr. Nadeau and some other analysts said the F.D.A. review was about as expected and was even in its tone, not leaning toward approval or against it. At noon, Orexigen shares were trading at $4.99, down about 9 percent.
Contrave is a combination of two existing drugs that help quell food cravings. One of them, bupropion, is an anti-depressant 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 side effects of the two component drugs – particularly the risk of seizures from bupropion – were also of concern to the F.D.A. reviewers of Contrave.
http://prescriptions.blogs.nytimes.com/2010/12/03/f-d-a-diet-pill-works-but-has-risks/?ref=health
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