Weight Loss Drug Gets New Review Date From FDA
Approval decision expected in September 2014
The FDA has extended its review of the resubmitted new drug application (NDA) for NB32 (Orexigen Therapeutics, Inc.), an investigational medication being evaluated for weight loss. The new Prescription Drug User Fee Act (PDUFA) action date has been set for September 11, 2014.
The FDA indicated that the review extension is needed to reach agreement on the post-marketing obligation related to the previously agreed upon evaluation of cardiovascular outcomes for NB32. The NDA resubmission package included interim safety and CV outcomes data from the ongoing 8,900-patient Light Study. Discussions about the package insert and other post-marketing obligations are ongoing.
NB32 is a fixed-dose combination of sustained-release bupropion and a proprietary sustained-release version of naltrexone, designed to improve drug tolerability.
Bupropion is thought to increase the level of dopamine activity at specific receptors in the brain, which appears to lead to a reduction in appetite and to increased energy expenditure by increasing the activity of pro-opiomelanocortin (POMC) neurons. Naltrexone works by blocking opioid receptors on POMC neurons, thereby preventing feedback inhibition of these neurons and further increasing POMC activity. In addition, NB32 may regulate activity in the brain’s dopamine reward system, which helps control food cravings and overeating behaviors.
In previous clinical trials involving more than 4,500 subjects, NB32 was shown to help people lose weight and keep it off for up to 1 year. In addition, in these studies, 53% of the participants taking NB32 and 21% of those taking placebo lost 5% or more of their body weight over the 12-month study period. Those who took NB32 for 6 months, combined with a structured weight management program, lost an average of 25 pounds compared with an average of 17 pounds for those using the weight management program and receiving placebo. Subjects who combined NB32 with diet and exercise experienced the greatest reductions in body weight.
NB32 was generally well tolerated in clinical trials. In the NB32 clinical development program, the most frequent adverse events were nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. These events were mostly transient and mild to moderate in severity.
NB32 is currently being evaluated in the Light Study, a randomized, double-blind, placebo-controlled, long-term research trial. The study is designed to assess the cardiovascular health outcomes of treatment with NB32.