AstraZeneca and Targacept, Inc., announced the enrolment of the first patient in the Phase 3 clinical development program for TC-5214, a nicotinic channel blocker. The Phase 3 program, referred to as the Renaissance Program, is designed to support the planned second half of 2012 filing of a new drug application with the U.S. Food and Drug Administration for TC-5214 as an adjunct treatment for major depressive disorder (MDD) in patients with an inadequate response to first-line therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin/norephinephrine reuptake inhibitor (SNRI). A Marketing Authorisation Application in Europe is planned for 2014.
AstraZeneca and Targacept have designed the Renaissance Program to include two fixed dose Phase 3 studies and two flexible dose Phase 3 studies to evaluate the efficacy and tolerability of TC-5214 as an adjunct treatment in patients with an inadequate response to SSRI or SNRI therapy. The Renaissance Program also includes a double blind, placebo controlled long-term safety study in which patients would receive TC-5214 or placebo for up to one year. All studies in the Renaissance Program are on track to initiate this year.
Each of the fixed dose and flexible dose Phase 3 studies includes an open label first phase in which patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to determine the extent of therapeutic response. For each study, patients who do not respond adequately based on predefined criteria are to be randomized into a double blind, placebo controlled second phase to receive a fixed dose (in the case of the fixed dose trials) or a flexible dose that may escalate (in the case of the flexible dose trials) of TC-5214 or placebo, twice daily, while continuing the SSRI or SNRI therapy for an additional eight weeks. The primary outcome measure for each study is change from double blind baseline for TC-5214 on the Montgomery-Asberg Depression Rating Scale (MADRS) as compared to placebo.
About TC-5214
Recent scientific evidence suggests that depressive symptoms are associated with an overstimulation of neuronal nicotinic receptors (NNRs) and other receptors in the brain that are activated by the neurotransmitter acetylcholine. This overstimulation is referred to as increased cholinergic tone. TC-5214 blocks certain NNR channels, which is believed to help normalize cholinergic tone resulting in antidepressant effects.
In 2009, Targacept completed a double blind, placebo controlled Phase 2b clinical trial of TC-5214 as an adjunct treatment in patients with MDD who did not respond adequately to first line therapy with the SSRI citalopram. In this study, TC-5214 outperformed placebo on the primary outcome measure (Hamilton Rating Scale for Depression-17) and all secondary outcome measures with statistical significance.
About the Collaboration Agreement between AstraZeneca and Targacept
In December 2009, AstraZeneca and Targacept signed a collaboration and license agreement for the global development and commercialization of TC-5214. The initial goal for the collaboration is to develop TC-5214 as an adjunct treatment for MDD in patients with an inadequate response to an SSRI or SNRI to regulatory approval. A Phase 2 clinical study to assess TC-5214 as a second line ("switch") monotherapy treatment for MDD is targeted to start in 2010.
About Major Depressive Disorder
MDD is a common illness, affecting approximately 42 million people worldwide, and the global antidepressant market is estimated to be approximately $20 billion. SSRIs and SNRIs are the most commonly prescribed classes of drugs for depression, but in many cases patients fail to respond adequately. In the NIMH's large-scale STAR*D study approximately 63% of patients did not achieve remission with first-line treatment with the SSRI citalopram hydrobromide.
About Targacept
Targacept is developing a diverse pipeline of innovative NNR Therapeutics™ for difficult-to-treat diseases and disorders of the nervous system. NNR Therapeutics selectively modulate the activity of specific neuronal nicotinic receptors, a unique class of proteins that regulate vital biological functions that are impaired in various disease states. Targacept's lead program, TC-5214, is in Phase 3 development as an adjunct treatment for major depressive disorder. Targacept leverages its scientific leadership and proprietary drug discovery platform Pentad™ to generate novel small molecule product candidates to fuel its pipeline, and uses its expertise to create significant alliances with global pharmaceutical companies. Targacept is committed to Building Health and Restoring Independence™ for patients. For more information, please visit www.targacept.com.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines. As a leader in gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease medicines, AstraZeneca generated global revenues of US $32.8 billion in 2009. For more information please visit: www.astrazeneca.com.