Orexigen obesity drug Contrave adds more Phase III success
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
Results from the remaining three studies in Orexigen's registrational program for its obesity drug Contrave (bupropion/naltrexone), released July 20, more than satisfy FDA's categorical efficacy benchmark for clinically significant weight loss, and the firm said it expects to submit the NDA in the first half of 2010. Rival weight-loss drugs Qnexa (phenterimine/topiramate) from Vivus and lorcaserin (APD-356) from Arena are expected to report Phase III data in the third quarter. Contrave, a fixed combination norepinephrine reuptake inhibitor and opioid receptor antagonist, is designed to address both the behavior and reward pathways in the brain to help patients initiate and sustain weight loss. In two of the three studies, 48 percent and 56 percent of patients, respectively, lost at least 5 percent of their body weight after 56 weeks, about three times the weight lost by the placebo groups. In the third study, in patients with type 2 diabetes, 44.5 percent of patients lost more than 5 percent of their body weight, more than double the 18.9 percent on placebo. They also experienced a 0.6 percent reduction in HbA1c from baseline compared to 0.1 percent in the placebo group. FDA guidance is that either the difference between the treatment group and placebo be at least 5 percent and statistically significant or that the proportion who lose at least 5 percent of their body weight be 35 percent and also double the proportion who lose 5 percent in the placebo group, the categorical benchmark. The fourth study, reported in January, met all of its endpoints and satisfied the categorical criteria, but the relative difference in absolute weight loss fell short of the first efficacy test, a lapse the company attributed to the stringent lifestyle and behavior modification program to which both the treatment and placebo groups were subjected (1"The Pink Sheet," April 6, 2009)
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Results from the remaining three studies in Orexigen's registrational program for its obesity drug Contrave (bupropion/naltrexone), released July 20, more than satisfy FDA's categorical efficacy benchmark for clinically significant weight loss, and the firm said it expects to submit the NDA in the first half of 2010. Rival weight-loss drugs Qnexa (phenterimine/topiramate) from Vivus and lorcaserin (APD-356) from Arena are expected to report Phase III data in the third quarter. Contrave, a fixed combination norepinephrine reuptake inhibitor and opioid receptor antagonist, is designed to address both the behavior and reward pathways in the brain to help patients initiate and sustain weight loss. In two of the three studies, 48 percent and 56 percent of patients, respectively, lost at least 5 percent of their body weight after 56 weeks, about three times the weight lost by the placebo groups. In the third study, in patients with type 2 diabetes, 44.5 percent of patients lost more than 5 percent of their body weight, more than double the 18.9 percent on placebo. They also experienced a 0.6 percent reduction in HbA1c from baseline compared to 0.1 percent in the placebo group. FDA guidance is that either the difference between the treatment group and placebo be at least 5 percent and statistically significant or that the proportion who lose at least 5 percent of their body weight be 35 percent and also double the proportion who lose 5 percent in the placebo group, the categorical benchmark. The fourth study, reported in January, met all of its endpoints and satisfied the categorical criteria, but the relative difference in absolute weight loss fell short of the first efficacy test, a lapse the company attributed to the stringent lifestyle and behavior modification program to which both the treatment and placebo groups were subjected (1 (Also see "Arena, Like Rivals, Greets Mixed Phase III Obesity Results With Brave Face" - Pink Sheet, 6 Apr, 2009.)). |