Orexigen’s Weight-Loss Drug Contrave Is Denied FDA Approval

Contrave, a novel weight-loss drug made by Orexigen.

In late January, in a surprise move to many in light of the positive FDA Advisory Committee meeting (see New Now Next in diaTribe #28), the FDA chose not to approve Orexigen’s weight-loss drug Contrave. As a reminder, Contrave is a combination of two currently approved drugs – naltrexone, used as a treatment for alcohol and opioid (e.g., morphine, heroin, codeine) addiction, and bupropion, an antidepressant and smoking cessation therapy. In human trials, participants taking Contrave averaged slightly less than 5% greater weight loss than those taking placebo (inert pills) over the course of a year, with those completing the trial averaging 8-11.5% depending on diet. However, though blood pressure was lower than at the start of the trial, those taking Contrave also experienced slight increases in heart rate and blood pressure when compared to placebo, raising possible concerns over potential unwanted cardiovascular side effects. A majority of the members of the FDA Advisory Committee who convened in December recommended that the FDA approve Contrave, advocating for a cardiovascular “outcomes” trial (a human study that assesses the long-term risks of a drug on the heart) to be held after approval – as opposed to before approval (for more details, please see New Now Next in diaTribe #28). While the vote appeared quite positive for Orexigen at the time, in a major and unexpected setback, the FDA is now requiring Orexigen to conduct an outcomes study for Contrave prior to approval. Although Orexigen has not determined how it will proceed, an outcomes trial will likely push the next possible approval date for the drug back at least two years – that is, if the company can afford it. Orexigen plans to work closely with the FDA to gain more information to determine the appropriate next steps for Contrave. All three late-stage obesity drugs have now received negative decisions from the FDA, requiring additional work before the agency will reconsider the drugs for approval. It is likely that these recent setbacks will discourage companies from developing weight loss therapies in the future, a disheartening prospect given the obesity epidemic. –VW