AstraZeneca, Targacept's depression drug candidate misses goal in second Phase III study
Tuesday, December 20 2011 | Comments
and Targacept Inc.
's investigational depression therapy, TC-5214 (S-mecamylamine), did not achieve the main endpoint in a second Phase III trial.
The release of the negative study data pushed Targacept shares down 35.9 percent.
The study, RENAISSANCE 2, is one of five randomized, double-blind, placebo-controlled trials being conducted as part of the clinical development program for TC-5214. The trial included 1,320 patients with major depressive disorder (MDD) who did not respond adequately to initial antidepressant treatment. Investigators evaluated the efficacy and tolerability of TC-5214 as an adjunct therapy to an antidepressant.
Of the patients who were screened, 710 initially received one of seven selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) on an open-label basis for eight weeks to determine the extent of therapeutic response.
After eight weeks, 319 patients who did not respond adequately were randomized into the double-blind phase of the trial and received a flexible dose of TC-5214 or placebo twice daily, while continuing their SSRI or SNRI therapy, for an additional eight weeks. TC-5214 was initially administered at a dose of 2 mg/day and could be increased at the discretion of the investigator to 4 mg/d and then 8 mg/d, based on tolerability and therapeutic response.
Top-line results from the study showed that the trial did not meet its primary endpoint, which was the change in the Montgomery-Asberg Depression Rating Scale total score after eight weeks of adjunct treatment with TC-5214 as compared with placebo.
Overall, TC-5214 was well-tolerated and had an adverse-event profile that was generally consistent with previous clinical trials of the drug.
AstraZeneca and Targacept said analyses of the full data set from RENAISSANCE 2 are ongoing.
Last month, the companies reported that TC-5214 also failed to meet the primary endpoint in RENAISSANCE 3, a similarly designed trial that included 624 patients with MDD.
The firms noted that their regulatory filing targets would be reviewed after results of the remaining RENAISSANCE studies become available. A potential New Drug Application filing for TC-5214 with the Food and Drug Administration
is planned for the second half of 2012.
Shares of Targacept closed at $4.99, down $2.79, in heavy trading on the Nasdaq.
This information concerns a use that has not been approved by the FDA.