FDA adds another weight loss drug to the US market

Combination therapy Contrave is the third weight loss drug to be approved by the US FDA in recent years.

Obese women in Louisiana, USA

A weight loss drug that combines two other medicines has been approved by the US Food and Drug Administration (FDA). Contrave comprises two drugs already approved for other indications: naltrexone, which is used against alcohol and opioid dependence, and bupropion, an antidepressant. 

The FDA approved Contrave for use in obese adults (body mass index of 30 or over) or overweight adults (BMI of 27 or over) with at least one weight-related condition such as high blood pressure, type 2 diabetes or elevated cholesterol on 10 September 2014. 

Patients taking the medicine should be evaluated after 12 weeks of treatment and patients who have failed to lose at least 5% of their body weight should discontinue the drug, it said.

The drug is currently under review by the European Medicines Agency (EMA) after its manufacturer, California-based Orexigen Therapeutics, submitted a marketing authorisation application in October 2013. In the UK, orlistat, a lipase inhibitor which reduces the absorption of dietary fat, is the only available anti-obesity agent, following the withdrawal of other products in the past 20 years, including sibutramine, dexfenfluramine and fenfluramine.

Available as extended release tablets, Contrave is the third weight loss drug that has been approved by the FDA in recent years. Belviq (lorcaserin), which acts on the brain to control hunger, and Qsymia (phentermine plus topiramate), which combines an appetite suppressant with anti-epilesy therapy, were approved by the FDA in 2012. These two products have not been approved in Europe. In 2013, the EMA rejected the marketing authorization for Qsiva (phentermine plus topiramate), while the manufacturer for Belviq withdrew its marketing application. 

Another product is also on the US horizon: on 11 September 2014, an FDA advisory panel recommended approval for Novo Nordisk’s diabetes treatment, liraglutide, as a treatment for obesity. Already known as Victoza, if approved, it will be marketed as Saxenda. 

Contrave was evaluated in several clinical trials that included around 4,500 obese and overweight patients, each of whom was treated with the drug for one year. In one trial, whose participants did not have diabetes, 42% of patients in the Contrave arm lost at least 5% of their body weight, compared with 17% in the placebo group. In another trial with diabetes patients, 36% of those treated with Contrave lost at least 5% of their body weight, compared with 18% of patients who received a placebo. 

The most common adverse reactions linked to Contrave are nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea. Blood pressure and heart rate should be measured prior to starting treatment and be monitored regularly, particularly among patients with controlled high blood press prior to treatment, the FDA says. 

As the product contains buproprion, the label will include a boxed warning alerting healthcare professionals and patients to the increased risk of suicidal thoughts and behaviours associated with antidepressant drugs.

Further caveats include not taking Contrave with other bupropion-containing drugs, and not administering it to patients who use opioids or treatments for opioid dependence, or who suffer from eating disorders. As Contrave can cause seizures, it must not be used in patients who have seizure disorders. 

Although Contrave has been approved, the FDA has issued a list of additional requirements. A cardiovascular-outcomes trial must be conducted to assess cardiovascular risk associated with use of the drug, while two efficacy, safety and clinical pharmacology studies in paediatric patients (one in patients aged 12–17 years and one in patients aged 7–11 years) must also be carried out. 

Orexigen says it does not fully understand how Contrave works. Nonclinical studies suggest that naltrexone and bupropion have effects on two separate areas of the brain involved in the regulation of food intake. These are the hypothalamus, which is the appetite regulatory center, and the mesolimbic dopamine circuit, also known as the reward system, it adds.

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Citation
The Pharmaceutical Journal, PJ, 20 September 2014, Vol 293, No 7828;293(7828):DOI:10.1211/PJ.2014.20066449