TC-5619 for Negative Symptoms and Cognitive Dysfunction in Schizophrenia, and Alzheimer’s Disease
TC-5619 is a novel small molecule that is highly selective for the alpha7 NNR. We are developing TC-5619 as a treatment for negative symptoms and cognitive dysfunction in schizophrenia, and are also evaluating potential additional development as a treatment for Alzheimer’s disease. In a Phase 2 study of TC-5619 that we completed previously in schizophrenia patients, TC-5619 showed a statistically significant benefit on the Scale for the Assessment of Negative Symptoms (SANS) and met protocol-defined success criteria on the study’s primary outcome measure, change from baseline on the Groton Maze Learning task of the CogState Schizophrenia Battery as compared to placebo.
Unmet Medical Need: Schizophrenia, which was estimated by the market research firm Decision Resources to affect approximately 4.7 million patients in the world's seven major pharmaceutical markets in 2011, is a chronic, severe and disabling form of psychosis. According to the National Institute of Mental Health MATRICS Consensus Statement on Negative Symptoms, persistent and clinically significant negative symptoms are an unmet therapeutic need in a large portion of schizophrenia cases, and it has been estimated that up to 75% of persons with schizophrenia are cognitively impaired. There are no drugs approved in the United States or Europe specifically for negative symptoms, cognitive dysfunction or residual symptoms in schizophrenia.
Decision Resources estimates that 20 million people have Alzheimer’s disease in the world’s seven major pharmaceutical markets, where treatment 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.
Pipeline Progress: We are currently conducting a Phase 2b study of TC-5619 that is evaluating the product candidate as a treatment for negative symptoms and cognitive dysfunction in schizophrenia at sites in the U.S. and Eastern Europe. This trial is a double blind, placebo controlled, parellel group study in schizophrenia patients with stable psychosis taking a fixed dose of an atypical antipsychotic. Following a four-week screening period, patients receive either one of two doses of TC-5619 (5mg or 50mg) or placebo, randomized in a 2:1:1 ratio (placebo:TC-5619 5mg: TC-5619 50mg). The primary outcome measure is change from baseline on the Scale for Assessment of Negative Symptoms (SANS). Key secondary outcome measures include the composite score on the CogState Schizophrenia Battery and the University of California, San Diego Performance-Based Skills Assessment, brief version.