FDA Approves Orexigen's, Takeda's Contrave For Weight Management

Orexigen Therapeutics announced in a press release that the Food and Drug Administration (FDA) has approved Contrave (naltrexone HCI and bupropion HCI), formerly NB32. Orexigen developed the weight management drug and licensed the commercialization rights in the U.S. to Takeda Pharmaceuticals.

Earlier in September, Orexigen announced that it was awarded a U.S. Patent for NB32 by the U.S. Patent and Trademark Office (USPTO). Michael Narachi, CEO of Orexigen, said, "Takeda has been a great, contributing partner throughout this endeavor, and we at Orexigen now look forward to doing everything possible to support them as they bring Contrave to the U.S. market."

Contrave

Contrave is an extended-release tablet that combines two FDA approved drugs. Naltrexone treats alcohol and opioid dependence while Bupropion treats depression, seasonal affective disorder, and helps patients stop smoking. The combination agent’s action mechanism is not fully understood. However, the drug appears to affect food intake through the hypothalamus and the mesolimbic dopamine circuit. Jean-Marc Guettier, M.D., director of the Division of Metabolism and Endocrinology Products at the FDA, said in its approval announcement, “Obesity continues to be a major public health concern. Contrave provides another treatment option.”

FDA Action

Orexigen submitted its application to the FDA for NB32 in 2011, but faced delays as recently as June 2014, when the FDA postponed its decision in order to evaluate cardiovascular (CV) outcomes. In its approval notification, the FDA noted common and uncommon side effects and adverse events. Common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. Seizures are a significant risk as are rises in blood pressure and heart rate.

The FDA has imposed significant responsibility on Orexigen in post-marketing requirements. The company must perform a cardiovascular outcomes trial, two efficacy, safety, and clinical pharmacology studies in pediatric patients, a nonclinical (animal) juvenile toxicity study, a cardiac conduction study, clinical studies on patients with hepatic or renal impairment, and a clinical trial on Contrave/other drug interactions. 

Efficacy Evidence

The FDA approved Contrave in part due to clinical trials establishing efficacy. Compared to a placebo group in which 21 percent lost five percent of their body weight, Contrave patients (50 percent) lost five percent of their bodyweight and kept it off for over 12 months. In a trial lasting six months, Contrave patients lost an average of 25 pounds.