Only one of three weight-loss pills that have come before the U.S. Food and Drug Administration this year has a hope of gaining the regulatory agency's approval, at a time when obesity is driving dual epidemics of heart disease and diabetes.
The medication, Contrave, passed a major hurdle on Tuesday when the FDA's Endocrine and Metabolic Drugs Advisory Committee voted 13-7 for approval. That leaves it to the agency to determine, most likely by the end of January, whether Contrave can be sold in the United States. The sustained-release formulation, designed to curb food cravings, combines two medications with long track records: the antidepressant bupropion (Wellbutrin, also sold as Zyban for smoking cessation), and naltrexone, prescribed for narcotic addiction and alcoholism.
Before Tuesday's hearing, Contrave had mixed support. It notably failed to meet one of the FDA's key benchmarks for determining weight-loss drug success. At minimum, a drug should lead to 5 percent more weight loss than a placebo. Study patients who took Contrave lost just 4.2 percent more weight than those given a dummy pill. However, the drug met another standard, with 30 percent of patients getting it losing at least 5 percent of their body weight.
During a day of testimony, the panel weighed the drug's modest weight-loss benefits against potential cardiac side effects, including elevated blood pressure that was most evident among diabetic study participants.
Heart risks were among side effects that led the FDA in October to kill Arena Pharmaceuticals' lorcaserin hydrochloride (Lorquess). The agency couldn't rule out cardiac effects when reviewing and ultimately rejecting Vivus Inc.'s Qnexa, a combination of the amphetamine phentermine and the anti-seizure drug topiramate that same month. Also in October, the FDA pulled Abbott Pharmaceuticals' sibutramine (Meridia) off the market because of increased heart attack and stroke risks. Meridia boosted blood pressure, heart rate and incidence of palpitations.
That leaves orlistat (Xenical) as the sole FDA-approved diet drug for sale in this country, although on May 26, 2010, the FDA said its label must spell out its potential to cause rare but severe liver damage.
The central dilemma in consideration of weight loss drugs comes down to determining how any excess risks they carry compare with the perils of sustained obesity or the risks associated with weight-loss surgery -- the only treatment currently found to be effective in the long run.
The current dearth of options has made the FDA "desperate to approve a weight-reduction drug, desperate for a magic bullet," said Dr. Sidney Wolfe, director of Public Citizen's Health Research Group in Washington, D.C. "One way of looking at it is the FDA's desperation to put another weight reduction drug on the market is increased because of these other two."
Wolfe said he would lead "a major effort to stop this drug from being approved." If approved, Contrave would be the first new obesity drug in more than a decade.
Wolfe contends that bupropion's known risks make Contrave dangerous. In an interview Wednesday, he said he hoped the FDA would learn a lesson from 1996, when it approved Meridia over objections raised by its advisory committee, only to take the drug off the market this year.
"The very reasons why Meridia should not have been approved are identical to this," Wolfe said.