TC-5619 is a novel small molecule discovered using our proprietary drug design technology known as Pentad (TM) that is highly selective for the alpha7 neuronal nicotinic receptor. TC-5619 has shown little or no interaction with 5HT3 receptors or hERG channels, both of which have historically been associated with significant side effects for other alpha7 NNR modulators.
In January 2011, we completed a Phase 2 clinical trial in which we assessed the effects of TC-5619 on cognitive dysfunction and negative symptoms in patients with schizophrenia. In the study, TC-5619 achieved statistical significance on the Scale for Assessment of Negative Symptoms (SANS), a secondary outcome measure, at 12 weeks. In addition, TC-5619 achieved predefined success criteria (Hochberg adjusted, one-sided p<0.1) on the study’s primary outcome measure, the Groton Maze Learning Task of the CogState Schizophrenia Battery (a measure of executive function). Other efficacy signals were observed sporadically across some of the study’s various other cognitive outcome measures. The results were generally driven by effects in tobacco-using patients.
In addition to the schizophrenia trial, we have completed a Phase 2 clinical trial of TC-5619 in adults with ADHD in which TC-5619 demonstrated activity in the patient population but did not achieve statistical significance on the primary outcome measure. We have also completed clinical and non-clinical studies designed to support the potential advancement of TC-5619 into Phase 2 clinical development for Alzheimer’s disease.
Based on outcomes to date, we are preparing for a planned Phase 2b clinical trial of TC-5619 as a treatment for residual (negative and cognitive) symptoms in schizophrenia, as well as for potential additional development in either or both of Alzheimer’s disease and ADHD.
About Residual Symptoms in Schizophrenia
Schizophrenia, which has been estimated to affect more than 4.6 million people in the world’s major pharmaceutical markets (United States, France, Germany, Italy, Spain, United Kingdom and Japan), is a chronic, severe and disabling form of psychosis. An estimated 80% of schizophrenic patients experience residual symptomatology, which includes both negative symptoms (e.g., a diminishment or absence of characteristics of normal function, including loss of interest in daily activities, lack of emotion and inability to plan or carry out activities) and cognitive dysfunction.1 There are no drugs approved in the United States or Europe specifically for negative, cognitive or residual symptoms in schizophrenia.
About ADHD
Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders. The principal characteristics of ADHD are inattention, hyperactivity and impulsivity. ADHD is a chronic disorder that develops during childhood, often persists into adulthood and can negatively impair many aspects of daily life, including home, school, work and interpersonal relationships. The market research firm Business Insights estimated that there were approximately 23.3 million adults and 21.6 million children and adolescents with ADHD in 2009 in the world's seven major pharmaceutical markets.
Current medications approved to treat ADHD include stimulants (e.g., amphetamine, methylphenidate), which are scheduled as controlled substances, and the non-stimulant atomoxetine. Because stimulants have potential for abuse, they are scheduled and can therefore be burdensome for patients. The currently available ADHD medications have a variety of side effects, including insomnia, increased heart rate, blood pressure and loss of appetite and behavioral changes such as irritability.
About Alzheimer's Disease
Alzheimer's disease is a progressive, degenerative disorder that attacks the brain's nerve cells, or neurons, resulting in loss of memory, thinking and language skills, and behavioral changes. The Alzheimer’s Association estimates that approximately 9.7 million people worldwide suffer from Alzheimer’s disease. In the United States, Alzheimer’s disease is estimated to affect more than 5.3 million people and the number of people age 65 and over afflicted with the disease is projected to increase by more than 50 percent to 7.7 million by 2030. The treatment of Alzheimer’s disease is dominated by acetylcholinesterase inhibitors. Acetylcholinesterase inhibitors have limitations in that only about half of Alzheimer’s patients who take them show symptomatic improvement, and they do not substantially delay the progressive cell deterioration that can lead to more severe impairment and debilitation.
1Schizophrenia (Decision Resources, January 2011)