Orexigen® Therapeutics is developing a new fixed dose sustained-release (SR) combination of naltrexone and bupropion for the treatment of obesity. The rationale behind the two active ingredients is stated to be:
- Bupropion acts on the weight control circuit by stimulating the POMC neuron.
- Naltrexone prevents inhibition of POMC neurons by blocking the action of Î²-endorphin
Bupropion is currently approved for the treatment of major depressive disorder (WELLBUTRIN) and as an aid to smoking cessation (ZYBAN). Naltrexone is indicated for the treatment of alcohol dependence (VIVITROL) and for the blockage of the effects of exogenously administered opioids (REVIA and several generics).
Orexigen states that the company followed the FDA guidance on weight loss products. Accordingly, the company conducted four phase 3 56 week, randomized, double-blind, placebo-controlled trials. The co-primary endpoints were the proportion of patients achieving at least 5% weight loss and percent change in body weight compared to placebo. According to company presentations, on an intent-to-treat basis, “[a]pproximately 25-33% lost 10% or more of their body weight and 12-16% lost at least 15%”. A summary of the Phase II and IIb and the four Phase 3 trials is here on pages 6-8 (also exploratory trials on smoking cessation and anti-depression in obese depressed patients). Yesterday, at the American Diabetes Association annual meeting, Orexigen presented results of 505 patient/52 site 56-week clinical trial that showed their proposed combination drug product helped diabetes patients lose weight and control their blood sugar better than a placebo.
The NDA was filed March 2010 and accepted for review by FDA on June 1, 2010. Orexigen recently announced that FDA’s Division of Metabolic and Endocrine Drug Products Advisory Committee Meeting is tentatively set for December 7, 2010 to review the NDA.
The weight-loss drug development community is going to learn a lot more about how FDA views this drug category by the end of the year. In addition to the Orexigen product, Vivus’s Qnexa® (phentermine/topiramate CR Capsules) will be reviewed July 15 and Arena’s Lorcaserin (a novel, single agent) is tentatively set for September 16.