Abstracts from the ASENT 2010 annual meeting March 4–6, 2010
Approved symptomatic therapies for Alzheimer's disease (AD) provide modest relief. In the future, it is likely that symptomatic treatments will be utilized with AD modifying therapies, the development of which are currently a primary focus of research. The nicotinic α7 receptor agonist may be an attractive drug candidate to potentially improve cognition in Alzheimer's disease patients either as a stand-alone therapy or in combination with other symptomatic treatments. EVP-6124 is a novel, potent, and selective α7 nicotinic receptor agonist. EVP-6124 has an excellent brain to plasma exposure ratio and has shown excellent efficacy and potency in a number of animal models of cognition. Four clinical studies in >125 healthy normal human subjects have been completed with EVP-6124, including a single-ascending-dose study, a 14-day multiple-ascending-dose study, a 21-day multiple-dose study, and a single-dose relative bioavailability, food, and gender effect study. EVP-6124 exhibited linear kinetics over the range of 1 to 180 mg and demonstrated a half-life suitable for once daily dosing. EVP-6124 appears to be safe and well tolerated for up to 21 days as measured by adverse events, vital signs, continuous cardiac monitoring, physical examination, and clinical laboratory evaluations. In addition, in normal volunteers, EVP-6124 demonstrated pro-cognitive effects (CogState testing) in various cognitive domains including executive function. These data suggest that EVP-6124 administered to AD subjects on stable cholinesterase inhibitor therapies may have potential benefit and that further study in this patient population is indicated. Larger phase II studies are currently being initiated in both Alzheimer's disease and schizophrenia.