FDA to Reconsider Once-Rejected Diet Drug

Feb 17, 2012 3:29pm

In the search for treatments to fight obesity, regulators are turning their attention to a diet drug that has already failed to receive government approval as a weight loss treatment.

Next week, a panel of advisors to the U.S. Food and Drug Administration will consider whether or not to recommend the diet drug Qnexa for approval. The move is the latest attempt to give new tools to patients and doctors to fight the obesity that currently plagues one-third of Americans. It also fans a fiery debate about the search for a “magic bullet” alternative to difficult lifestyle changes to help obese people lose weight.

Qnexa was rejected by the FDA in 2010 over concerns about potentially dangerous side effects, such as cardiovascular problems and birth defects. Now, the FDA will consider whether or not the drug’s manufacturer, Vivus, should do a larger clinical trial to investigate the potential for cardiovascular side effects.

But some obesity specialists are, in effect, already giving the drug to their patients by prescribing Qnexa’s two major ingredients, phentermine and topiramate. The practice, called off-label prescribing, is not prohibited by the FDA. Doctors who have prescribed this combination say it has helped patients shed pounds when many other paths to weight loss have failed.

Dr. Ken Fujioka, director of the Center for Weight Management at Scripps Clinic in San Diego, said he often sees obese patients who have changed their diets, started exercising more and still have not been able to lose more than a few pounds. Though bariatric surgery is a lasting, effective option for long-term weight loss, many patients either aren’t morbidly obese enough to qualify for the surgery or are reluctant to resort to such a drastic measure to lose weight. For about 30 of these patients, Fujioka has prescribed low doses of phentermine and topiramate.

“The weight loss with this combination rivals bariatric surgery and I see using these meds in the seriously obese patient as an alternative,” Fujioka said.

Dr. Jana Klauer, a New York City-based doctor specializing in weight management, said her patients lost an average of 40 pounds when taking the drugs along with improved diet and exercise plans.

“The drug combination gives great results, providing diet and exercise are part of the plan,” she said.

Vivus, the company that developed Qnexa, said in a statement that the drug is a combination of low doses of both drugs and it is intended for use in combination with improvements in diet and exercise. Vivus said it does not support the off-label use of phentermine and topiramate.

The drugs work by suppressing appetite, and both have been approved by the FDA for other uses. Phentermine, a stimulant, is already approved for weight loss, but only for short-term use. Topiramate is an anticonvulsant, for which weight loss is a side effect.

But a laundry list of side effects has many experts concerned about the safety of the drugs, if taken over a long period of time. Topiramate creates feelings of mental fogginess, memory lapses and a lack of concentration.

Phentermine, one of drugs that made up the failed diet drug Fen-Phen, can lead to a range of cardiovascular side effects, such as high blood pressure, heart attacks and heart palpitations. Dr. David Katz, co-founder of the Yale University Prevention Research Center, noted that these side effects are the very problems caused by obesity.

Dr. Charles Clark, a professor of pharmacology and toxicology at Indiana University, said the potential side effects are enough to keep him from prescribing phentermine and topiramate to his patients, particularly in light of the failure of Fen-Phen, which was withdrawn from the market in 1997 after causing fatal blood pressure and heart valve problems in patients.

“Given our experience with Fen-Phen, we should be cautious in our use of these agents until larger and longer-term trials are completed,” Clark said.

Others say concerns about side effects of both drugs and their offspring Qnexa are legitimate, but could be managed or avoided if doctors carefully monitor patients while they’re taking the drug. For example, the FDA’s concerns about potential birth defects caused by Qnexa could be resolved by not prescribing the drug to women who could get pregnant. Many doctors say the risks of these drugs may be outweighed by the benefits for some patients with disabling health problems caused by obesity.

In the past 20 years, a parade of diet drugs have come before the FDA, representing an effort by drug companies to give obese patients and their doctors alternatives to difficult, often unsuccessful lifestyle changes. Most of the drugs have failed to meet the agency’s standards for safety and effectiveness. Many come with a list of embarrassing side effects, such as anal leakage, and only one, Alli, is approved for long-term use. A handful of drugs, such as Metabolife and Meridia, were removed from the market because of heart safety concerns.

Some doctors say there is no evidence that Qnexa will perform better than the diet drugs that have already flopped.

“I have made selective use of some weight loss drugs, but have not to date found much reason for enthusiasm for any of them,” Katz said. “I don’t have much for Qnexa.”

Others are more hopeful that Qnexa is different, including Dr. Chip Lavie, medical director of cardiac rehab and prevention at the Ochsner Clinic Foundation in New Orleans. He cites evidence from previous clinical trials that Qnexa helps patients lose a modest amount of weight, which improves their risk factors for diabetes, high blood pressure and other cardiovascular problems. He said cardiovascular and birth defect risks that the FDA cited in its first look at the drug were very slight and “clinically unimportant.”

“Considering the dismal results that many experience with attempted weight loss with diet and exercise, which is always the first choice, and the explosion in the need and use of bariatric surgery, this combination drug should be a major advance, and I hope that it gets approved this time by the FDA,” Lavie said.

ABC News’ Dr. Richa Shukla contributed to this report.

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