FDA Approves New Obesity Drug, First Obesity Approval Since 2012

The FDA approved naltrexone hydrochloride and bupropion hydrochloride extended-release (ER) tablets (Contrave) as treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity. This is the third US approved obesity medication and the first to be approved since 2012.

The drug is approved for use in adults with a body mass index (BMI) of ≥30 or a BMI of ≥27 with at least 1 weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia.

Manufactured by Orexigen Therapeutics Inc, naltrexone hydrochloride and bupropion hydrochloride ER is a combination of the antidepressant bupropion and a formulation of naltrexone, which is designed to prevent drug dependence. The company did not say when the pill would become available or how much it would cost.

The effectiveness of naltrexone hydrochloride and bupropion hydrochloride ER was evaluated in multiple clinical trials that included approximately 4500 obese and overweight patients with and without significant weight-related conditions who were treated for 1 year. All patients received lifestyle modification that consisted of a reduced-calorie diet and regular physical activity.

Results from a clinical trial that enrolled patients without diabetes showed that patients had an average weight loss of 4.1% compared with patients who received placebo at 1 year follow-up. In this trial, 42% of patients treated with naltrexone hydrochloride and bupropion hydrochloride ER lost at least 5% of their body weight compared with 17% of patients treated with placebo. Results from another clinical trial that enrolled patients with type 2 diabetes showed that patients had an average weight loss of 2% compared with patients receiving placebo at 1 year follow-up. In this trial, 36% of patients treated with naltrexone hydrochloride and bupropion hydrochloride ER lost at least 5% of their body weight compared with 18%of patients treated with placebo.

Patients using naltrexone hydrochloride and bupropion hydrochloride ER at the maintenance dose should be evaluated after 12 weeks to determine if the treatment is working. If a patient has not lost at least 5% of baseline body weight, use of the drug should be discontinued.

Because naltrexone hydrochloride and bupropion hydrochloride ER contains an antidepressant, it will carry a warning about increased risk of suicidal thoughts and behaviors. Naltrexone hydrochloride and bupropion hydrochloride ER can also cause seizures and must not be used in patients who have seizure disorders. The risk of seizure is dose-related. Naltrexone hydrochloride and bupropion hydrochloride ER can also raise blood pressure and heart rate and should not be used in patients with uncontrolled high blood pressure.

Other products containing bupropion should not be taken with naltrexone hydrochloride and bupropion hydrochloride ER. Naltrexone hydrochloride and bupropion hydrochloride ER should also not be taken by patients who are using opioids or treatments for opioid dependence, or who are experiencing acute opiate withdrawal.

The most commonly reported adverse reactions include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.

The FDA is requiring a number of post-marketing studies, including a cardiovascular outcomes trial, pediatric use, and renal and hepatic impairment outcomes trial, in addition to others.

The FDA originally delayed the decision on the drug in June due to concerns regarding adequate warnings on the packaging.

Sales for naltrexone hydrochloride and bupropion hydrochloride ER are expected to reach $200 million in 2016.

Reimbursements for obesity medications are expected to remain a challenge for the foreseeable future until insurers are convinced they can be justified even without improvements in cardiovascular health.—Kerri Fitzgerald