The first Phase III study evaluating Targacept and partner AstraZeneca’s nicotinic channel modulator TC-5214 failed to meet its primary endpoint. The Renaissance 3 study was evaluating use of TC-5214 as an adjunct to antidepressant therapy in patients with major depressive disorder (MDD) who don’t respond adequately to initial antidepressant treatment. Data from the trial showed that adding TC-5214 to antidepressant treatment failed to result in a change on the Montgomery–Asberg Depression Rating Scale (MADRS) after eight weeks of treatment.
The European Renaissance 3 study included 624 patients with MDD who initially received one of seven SSRI or SNRI antidepressants on an open-label basis for eight weeks. Two-hundred ninety-five patients who didn’t respond to treatment were randomized to a double-blind phase and received either a physician-prescribed flexible dose of TC-5214 or placebo, while continuing on SSRI or SNRI therapy for another eight weeks.
The Renaissance program will include another flexible-dose study (Renaissance 2) and two fixed-dose studies (Renaissance 4 and 5) that will evaluate the efficacy and tolerability of TC-5214 as an adjunct to SSRI/SNRI therapy. A fifth study, Renaissance 7, is a long-term safety study evaluating the adjunctive use of TC-5214 for a year. In February the firms started a 350-patient Phase IIb study investigating TC-5214 as a “switch” monotherapy for MDD patients who don’t respond adequately to initial antidepressant therapy. Patients who do not respond adequately to open-label treatment with one of six commonly used SSRI or SNRI antidepressants will be switched to receive either one of two fixed doses of TC-5214, the active control duloxetine, or placebo, for eight weeks.
AstraZeneca and Targacept inked their global development and commercialization deal for TC-5214 back in December 2001. Under terms of the agreement Targacept received a $200 million up-front payment and could earn another $540 million in development, regulatory, and commercial milestones, plus up to $500 million in sales milestones. The firm has retained an option for co-promotion of TC-5214 to a limited target physician audience in the U.S.