Based on positive results of the interim analysis of the Light Study, Orexigen Therapeutics, Inc will resubmit the Contrave® New Drug Application (NDA) to the United States Food and Drug Administration (FDA) in the next few weeks with potential approval by June 2014. 

The Contrave Light Study is a double‐blind, placebo‐controlled cardiovascular outcomes trial that randomized approximately 8,900 patients. The primary objective of the Light Study, which Orexigen is conducting at approximately 260 clinical sites in the United States, is to rule out excess cardiovascular risk in overweight and obese patients receiving Contrave. 

Contrave (naltrexone sustained release (SR)/bupropion SR, hereafter naltrexone/bupropion) is an investigational medication being evaluated for weight loss. Prior to initiation of the Light Study, naltrexone/bupropion was studied in clinical trials enrolling more than 4,500 people. Naltrexone/bupropion has been shown to help people lose weight and keep it off for up to one year. In previous clinical trials, 53 percent of study participants taking naltrexone/bupropion and 21 percent of those taking placebo lost five percent or more of their body weight over the 12 month trial duration. Many patients saw noticeable improvements in cholesterol levels, and blood sugar control, as well as smaller waistlines. Those who combined naltrexone/bupropion with diet and exercise experienced the most reduction in body weight. There is no guarantee that naltrexone/bupropion will make patients lose weight.

Naltrexone/bupropion was generally well tolerated in earlier clinical trials. In the Contrave Phase 3 clinical development program, the most frequent adverse events on naltrexone/bupropion were nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. These were mostly mild to moderate in severity and did not last long.

The FDA previously agreed that if the interim analysis would meet the specified criteria to exclude cardiovascular risk, Contrave could be approved. The pre-specified criteria for the interim analysis is to exclude a hazard ratio of 2.0, using the upper bound of the 95% confidence interval, for excess risk of major adverse cardiovascular events (MACE) in patients receiving naltrexone/bupropion as compared to placebo. In addition to meeting the pre-specified criteria for excluding cardiovascular risk, no new safety signals were observed.

"The resubmission will contain an unprecedented amount of cardiovascular outcomes data for an obesity therapeutic, and we are confident these data will support a favorable benefit:risk assessment for Contrave," said Michael Narachi, CEO of Orexigen.  

Source: press release Orexigen November 25 2013