Orexigen and partner Takeda will be breathing a huge sigh of relief after the US Food and Drug Administration finally approved their weight loss pill Contrave (naltrexone/bupropion).

The drug has been cleared for use in adults who have a body mass index (BMI) of 30 or greater (obese) or 27 or greater (overweight) and at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol.

Contrave combines naltrexone, which is also approved in the US to treat alcohol and opioid dependence, and the antidepressant bupropion. Approval comes on the back of clinical trials involving more than 4,500 obese and overweight patients, showing its weight loss benefits. In one study involving patients without diabetes, 42% of those given Contrave lost at least 5% of their body weight compared with 17% of those treated with placebo, while another trial with type II diabetics showed that 36% cut at least 5% of their body weight versus 18% of the control group.

On the safety side, because it contains bupropion regulators have slapped Contrave with a boxed warning on the increased risk of suicidal thoughts and behaviours. The labelling also notes that the pill can cause seizures and can raise blood pressure and heart rate, and so must not be used in patients with uncontrolled high blood pressure.

Indeed, despite its approval the FDA still has questions over the drug’s safety, prompting the agency to set out a long list of post-marketing requirements, including: a cardiovascular outcomes trial; two efficacy, safety, and clinical pharmacology studies in paediatric patients; and clinical trials to evaluate dosing in patients with hepatic or renal impairment.

Third to make it

After initially being rejected in 2011 over a deficiency related to cardiovascular safety, Contrave has now become the third obesity drug allowed entry to the US market in more than 10 years, following in the footsteps of both Vivus' Qsymia (phentermine/topiramate) and Arena/Eisai's Belviq (lorcaserin), which have thus turned in a somewhat lacklustre performance.

Nevertheless, Wells Fargo analyst Matthew Andrews is reportedly expecting Contrave’s US sales to overshoot that of Belviq and Qsymia by 2016, coming in at around $200 million compared to Belviq’s $180 million and Qsymia’s $150 million, with a helping hand from Takeda’s substantial marketing muscle.

But there are also others snapping at its heels. Novo Nordisk is gearing up for a US launch of its once-daily human GLP-1 analogue obesity treatment, a high-dose form of its diabetes drug Victoza which is to be marketed as Saxenda. While it is yet to receive official FDA clearance things are looking good for the drug; an advisory panel has today voted 14-1 in favour of its approval.