An independent panel of FDA advisors on Thursday voted narrowly to recommend against approval of a proposed new weight-loss drug, Qnexa. The drug agency, which is expected to make an up or down decision on the drug by October, is not bound by the advisory panel's 7-9 recommendation against approval. But the panel's views generally weigh heavily in the agency's final decision.
In the race among pharmaceutical companies to win market approval for a new generation of obesity drugs, Qnexa is the most recent to make it to the crucial FDA advisory panel stage. It's the first of a trio of new candidate drugs to do so. (The others, lorcaserin and Contrave, are to come before an FDA advisory panel in September and December, respectively.)
Qnexa, developed by the biotechnology firm Vivus of Mountain View, Calif., combines phentermine, a stimulant that has been used in the past for weight loss, and topiramate, a medication that has been approved to treat seizure disorders and migraines.
Other candidate weight-loss drugs — most recently rimonabant — have failed to make it over the hurdle the FDA set in 2007 to guide its consideration of future weight-loss drug candidates.
The FDA is walking a tightrope in its deliberations on weight-loss drugs. With two-thirds of American adults overweight or obese and a resulting public health disaster looming, the agency urgently needs to approve a medication that can help Americans lose weight and keep it off. At the same time, the agency is acutely aware that any weight-loss product it approves will probably be broadly marketed and taken by a potentially vast population of patients already beset by obesity-related conditions. Given those circumstances, any hint of a drug-related safety problem could quickly mushroom.
The FDA's staff report on Qnexa, posted this week to the FDA's website, reflected the delicate balance the agency is striking. Looking at Qnexa's performance in two clinical trials sponsored by Vivus, the FDA's staff found a somewhat effective weight-loss drug with a worrying array of side effects.
Qnexa's performance as a weight-loss drug just got over the bar the FDA has set for effectiveness in weight-loss drugs. The staff report declared Qnexa "efficacious for weight loss." But it noted that the different rates at which subjects on a placebo drug and those on Qnexa lost 5% of their body weight "were of nominal statistical significance." Among those on the mid-dose and highest doses of Qnexa, 62% and 69%, respectively, lost 5% of their body weight.
And the drug's safety record during clinical trials — particularly at high doses, at which it's most effective — will clearly raise questions about how it would affect a broad population of overweight and obese patients, if it's approved for broad use.
Twice as many subjects taking the highest dose of Qnexa withdrew from clinical trials, citing side effects, than those taking the placebo. At high doses, subjects reported such side effects as palpitations, anxiety, thoughts of suicide and difficulty in concentrating at far higher rates than those taking a placebo. Four heart attacks were reported among the roughly 2,280 subjects being treated with Qnexa, but none was reported among those taking the placebo.
Finally, the FDA's staff expressed concern over the safety of Qnexa for women who might become pregnant, given that one of the drug's components has been shown to cause birth defects. In the clinical trials the staff reviewed, women on birth control taking Qnexa appeared more likely than similar women taking placebo to get pregnant. That finding prompted the FDA's staff to wonder whether Qnexa might render some prescription birth-control methods less effective.