Orexigen Therapeutics Inc. will tell the FDA advisory panel on metabolic and endocrinological drugs that in four different clinical trials, subjects taking Contrave -- a combination of the antidepressant bupropion and the anti-addiction drug naltrexone -- lost more weight than did those taking a dummy pill.
The FDA staff's memo, posted to the FDA website ahead of Tuesday's meeting, notes that in four clinical trials with a total of roughly 4,500 overweight and obese subjects, the weight-loss differences between those taking Contrave and those taking a placebo for roughly a year were "of nominal statistical significance." But the proposed diet drug did satisfy a backup measure of adequate effectiveness the FDA said it would consider: in all four trials, more than a third of subjects lost a total of at least 5% of body weight while taking Contrave. In one of the four, two-thirds lost more than 5% of their body weight, and on average, roughly half did in the other trials.
But because one of the drugs in the investigational medication -- bupropion -- elevates blood pressure, cardiovascular side effects are a concern, the FDA staff wrote. Rates of blood pressure-related "adverse events" were significantly higher among subjects taking Contrave than among those taking placebo, although the staff report says there were not enough to make predictions of how many would be so affected in a larger population.
Contrave, however, is meant to be taken -- possibly for years -- by obese patients, who are already at higher risk of high blood pressure and strokes. So this side effect will likely raise concern among advisory panelists. The staff memo said the FDA and Orexigen are "in the early stages of discussing" how to measure the drug's cardiovascular risk. The panel could recommend that study be completed before the FDA approves marketing of Contrave, or they could recommend it be done after the drug hits the market.
Other concerns flagged were the component bupropion's association with seizures in some patients, and worries that it can induce suicidal thoughts, especially soon after a patient has started the drug.
The FDA's advisory panelists have shown a strong conservative streak in weighing the risks and benefits of diet drugs. In 2007, they recommended strongly against approval of the European diet drug rimonabant, effectively nixing its prospects. In June and October of this year, the panel meeting Tuesday recommended against approval -- at least for now -- of two other diet drugs, Qnexa and Lorcaserin, respectively.