April 11, 2011— -- Mary Williams wanted to lose weight and was ready to do the work.
"With a 5" 5' frame, 215 pounds was just too much," Williams said. "I looked like the Nutty Professor."
She tried dieting and exercising. She even tried phentermine, a drug approved for short-term weight loss, which helped her lose a measly four pounds.
Uninterested in bariatric surgery, Williams said she worried she had run out of options until a clinical trial at Duke University in Durham, N.C., opened a new door.
A daily dose of Qnexa -- an experimental weight loss drug that combines phentermine with topiramate, a drug approved for epilepsy and migraine prevention -- along with a diet and exercise helped Williams drop 38 pounds and six dress sizes in a year.
"When I would visit with friends and colleagues they would say, 'Something has changed, you've lost weight.' They were so impressed," Williams said.
The average percent weight loss among 995 patients who received Qnexa in the phase 3 trial was 9.8 percent, compared to 1.2 percent among 994 patients who received a placebo. The trial findings were published April 9 in The Lancet.
But despite the promising results, the Food and Drug Administration rejected an application from drug maker Vivus to have Qnexa approved for the treatment of obesity, citing safety concerns. Qnexa was associated with a low but increased risk of psychiatric and cardiovascular adverse events. The FDA also wants Vivus to investigate the potential for Qnexa to cause birth defects.
"As clinicians and clinical researchers, we'd all consent that the FDA seem to have set a very different safety bar for drugs that treat weight loss compared to drugs that treat other conditions," said Dr. Kishore Gadde, director of Duke's obesity clinical trials program and lead author of the study.
Qnexa was one of three weight loss drugs nixed by the FDA in 2010.
"We need more options to treat obesity," Gadde said. "In hypertension, you have about 40 to 50 drugs with different mechanisms. In obesity, when you try diet and exercise and it doesn't work, you only have one drug before you jump to last resort, which is surgery."
The single drug approved for the treatment of obesity -- orlistat (Xenical or Alli) -- acts by preventing the absorption of dietary fat. But it doesn't quash hunger.
"People know they should cut down on calories. But if you only have orlistat, how do you deal with a patient who comes to you and says, 'I know all this stuff but I cannot control my hunger?' For that patient orlistat won't work," Gadde said.
Williams said Qnexa helped her feel less hungry and more energetic -- a combination that helped her eat less and exercise more. After the trial ended, Williams started to gain some of the weight back.
"I do get a little lazy sometimes and do want to eat some of the goodies I see before me," Williams said.
New Hope for Weight Loss Drug?
Vivus is in talks with the FDA to address any outstanding safety concerns, according to company president Peter Tam.
"We're working diligently to resubmit the drug application," Tam said. "We believe in this drug."
Gadde and Tam said they think the FDA is being hard on weight loss drugs because of the number of Americans who would use them.
"Ultimately safety is the most important thing from FDA's perspective," Tam said. "For a drug like this that could be used by many Americans, safety has to be scrutinized."
The FDA recently lowered the bar for lap band surgery, potentially expanding the eligibility from 13 million Americans to nearly 32 million -- a move Tam hopes reflects some urgency within the FDA to do something about obesity.
"I think it's all about risk-benefit assessment," Tam said. "And [Qnexa] is a drug that has demonstrated a tremendous amount of benefit."
Williams said she hopes the FDA will allow clinicians to weigh the risks and benefits of the drug for their patients.
"My doctor wants me to lose another 20 pounds," Williams said. "It would be helpful for me if the FDA would pass it."