TC-5214
TC-5214 is a nicotinic channel blocker that modulates the activity of a number of various NNR subtypes. We are currently conducting development of TC-5214 as an augmentation therapy for major depressive disorder, or MDD, and as an augmentation therapy for resistant hypertension. It is well known that depressive symptoms can result from an overstimulation of NNRs and other receptors in the brain that are activated by the neurotransmitter acetylcholine. Accordingly, compounds capable of inhibiting the activity of these overstimulated receptors may potentially have antidepressant effects. In July 2008, we initiated a Phase 2b clinical trial of TC-5214 in subjects with MDD who do not respond well based on predefined criteria to first-line treatment with citalopram hydrobromide, a marketed antidepressant from the drug class known as selective serotonin reuptake inhibitors. It is also well established that nicotinic channel blockers that inhibit activity of NNRs in the peripheral nervous system can have anti-hypertensive effects. However, these agents activate compensatory mechanisms in the body that, over time, can offset the intended beneficial effects. A number of currently available medications are known to block these mechanisms, but these medications alone are not sufficient to control blood pressure for treatment resistant patients. The use of a nicotinic channel blocker to augment existing medications may have the potential to achieve blood pressure targets for these patients. In April 2009, we initiated a Phase 2 exploratory study of TC-5214 in subjects with resistant hypertension.
About Major Depressive Disorder
According to The National Institute of Mental Health (NIMH), MDD is the leading cause of disability in the United States for people between the ages 15 and 44. The NIMH estimates that approximately 14.8 million American adults suffer from MDD.
The Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study undertaken by the National Institute of Mental Health between 2001 and 2006 showed the inadequacy of currently available therapies for MDD. In the first phase of the STAR*D study, approximately 2,800 persons with MDD were given citalopram for 12 to 14 weeks. Only about one-third of the participants reached remission and about 10-15 percent more responded, but did not reach remission. The second phase of the STAR*D study evaluated the effects of augmentation with a new medication or switching to a different treatment for participants who did not respond or only responded partially to citalopram. Approximately one in four of these participants reached remission. These findings have been cited as highlighting the need for more broadly effective antidepressant treatments (Rush, et al., NEJM Volume 354:1231-1242, March 23, 2006 Number 12).
About Resistant Hypertension
Hypertension, or high blood pressure, leads to an increased risk for life threatening cardiovascular events such as heart attack, stroke and congestive heart failure. The American Heart Association estimates that hypertension affects about 73 million people in the United States age 20 and older. Although the exact prevalence is unknown, it has been projected that approximately 10 million patients in the United States are impacted by resistant hypertension. Resistant hypertension, also sometimes called refractory hypertension, occurs where high blood pressure is not returned to within normal ranges with the use of three anti-hypertensives from different drug classes, including a diuretic.