SILVER SPRING, Md. -- An FDA advisory committee has voted 13-7 that the modest weight-loss benefits of an investigational combination of naltrexone and bupropion -- marketed under the brand name Contrave -- outweigh the drug's blood pressure risk.
The bupropion-naltrexone combo is the last in a trio of new weight-loss drugs that went before FDA panels this year, striving to be the latest treatment in the dwindling field of medications to fight obesity. The previous two drugs, phentermine/topiramate (Qnexa) and lorcaserin hydrochloride (Lorqess) were both rejected by the FDA after they fared poorly at advisory committee meetings.
But Tuesday's advisory committee ended very differently than the previous two.
Bupropion/naltrexone appeared to offer fewer side effects than the previous two drugs, although it also doesn't appear to work as well at helping obese patients lose weight.
The FDA will make an approval decision by Jan. 31. The agency does not have to follow the advice of its advisory committees, but it often does.
Orexigen, the company that makes naltrexone/bupropion in partnership with Takeda, is seeking approval for treatment of obesity and weight management in patients with a body mass index of 30 or above, or 27 or above and with one or more risk factors, such as diabetes, dyslipidemia or hypertension.
Contrave combines an antidepressant and an anti-addiction drug, both of which have been used individually for 20 years -- naltrexone for opioid addiction and alcohol dependence and bupropion for depression and smoking cessation. However, little is known about combining the drugs for weight managment.
The Endocrine and Metabolic Drugs Advisory Committee reviewed results from Orexigen's four placebo-controlled, one-year, phase III clinical trials, which enrolled 3,200 obese patients with at least one comorbid condition, including diabetes and depression.
In all four trials, patients on the naltrexone/bupropion combination lost more weight than those in the placebo group (P<0.001), and more than 30 percent lost at least 5 percent of their body weight, which is one standard by which the FDA judges efficacy of weight-loss drugs.
In a pooled analysis, naltrexone/bupropion patients lost an average of 4.2 percent more weight than the placebo group (ranging from 3.3 percent to 4.8 percent). That falls short of the other FDA standard that after one year, the difference in mean weight loss between the active and control groups should be at least 5 percent.
In one trial where patients taking naltrexone/bupropion were compared with those undergoing a lifestyle modification program, the difference between the groups was even smaller, suggesting that diet and exercise can achieve similar results as naltrexone/bupropion.
"As far as efficacy goes, I think they made it by the hair of their chinny chin chin," said Melanie Coffin, the panel's patient representative.
In the FDA's assessment of the drug released last week, reviewers expressed concerns over several side effects -- a potential increased risk for dizziness, nausea, seizures, and high blood pressure among patients taking naltrexone/bupropion.
However, the panel was mostly just concerned with one side effect: The drug's effect on blood pressure.
In the trials, patients taking naltrexone/bupropion were more likely to have an increase in blood pressure and heart rate than placebo patients, an effect that was most pronounced during the first eight weeks of treatment.