July 15, 2010 -- Don't approve Qnexa for weight loss, an FDA expert advisory panel today said in a 10-6 vote.

The panel of medical experts found Qnexa effective but worried about millions taking it before safety concerns are answered.

The FDA usually follows the recommendation of its advisory panel, but the split vote, and some of the comments by panelists, may leave the FDA room to approve the drug.

"I hope my 'no' vote will allow more discussion. I would not be upset if it were approved with more indications [limiting its use]," said panel chair Kenneth Burman, MD, of Georgetown University.

With the rest of the panel, Burman agreed that Qnexa works better than any approved weight loss drug. While people taking it don't get thin, they do lose 6% to 10% of their body weight -- if they also undergo a program of diet and exercise.

But the drug has side effects, both known and theoretical. It may cause birth defects, it may increase suicide risk, it can cause a condition called metabolic acidosis that speeds bone loss, it increases risk of kidney stones, and may have other serious effects.

"It is difficult if not impossible to weigh these issues as the clinical trials went on only for a year, and patients will use this drug for lifetime," Burman said. "It is impossible to extrapolate the trial data to the wider population."

Even so, the FDA was listening to Burman and other panelists who said their vote against approval was a close call.

"When you listen to even the 'no' voters, you got the sense a lot of people had a little bit of hesitancy," FDA Deputy Director for Endocrine Products Eric C. Colman, MD, said in a news conference. "They were not strongly against the drug but had lingering concerns that made them vote 'no.'"
Potential for Widespread Use

Qnexa is a combination of low doses of two drugs already on the market: the amphetamine phentermine and the seizure drug topiramate.

It's targeted for use only by obese patients and in overweight people with a BMI of 27 or more plus a weight-associated condition such as high cholesterol, type 2 diabetes, or high blood pressure. But panelists worried that millions of people struggling with their weight will want to give the drug a try.

They worry because both phentermine and topiramate have serious side effects. Phentermine is the "phen" half of the failed weight-loss drug fen-phen, although that drug's heart toxicity was almost entirely due to its "fen" half. Topiramate is linked to attention and memory problems, and to depression and suicidal thoughts. It also causes birth defects in lab animals.

The panel vote came as a bitter disappointment to trial participants who testified at the panel hearing. One was Margaret I. "Peggy" Pence, a military veteran and horse farmer.

"I weighed 200 pounds. After 15 months on Qnexa I weighed 143, and went from a size 20 to a size 10," she said. "My brain quit nagging me about food. I immediately became a person who quit snacking and ate healthy meals."

But others, such as Sidney Wolfe, MD, health director for the consumer group Public Citizen, worry that Qnexa is too dangerous for widespread use.

"There is every reason to believe a drug like this will be used by millions. For safety reasons, this drug should not be approved," Wolfe told the panel. "This is not a new therapy. It is just a repackaging of old ones that have significant dangers."