AZD1446 (TC-6683) and AZD3480 (TC-1734) are novel small molecules that act selectively on the alpha4beta2 NNR subtype. We have granted to AstraZeneca an exclusive license for the worldwide development and commercialization of AZD3480 and AZD1446 for various conditions characterized by cognitive impairment under a 2005 collaborative research and license agreement.
AZD1446 is the most advanced product candidate arising out of a now completed preclinical research collaboration that we conducted with AstraZeneca and is under consideration for potential future development in Alzheimer’s disease. As of October 2010, AstraZeneca has completed three of four early clinical studies of AZD1446 expected to inform an advancement decision in the coming months. AstraZeneca is responsible for executing and funding all development and commercialization of AZD1446.
In a Phase 2 trial in adults with ADHD, no drug effect was seen on the primary outcome measure, the Conners’ Adult ADHD Rating Scale-Investigator Rated Total ADHD Symptoms score (CAARS-INV) and, based on this result, further development in ADHD is unexpected. Positive results were obtained in the study in non-nicotine users on three of five tasks of the CogState computerized test battery, secondary outcome measures designed to assess important cognitive functions such as learning and memory. AZD1446 did not demonstrate similar superiority at any dose on the CogState tasks in the nicotine user dataset. Other secondary outcome measures of the study did not demonstrate a drug effect.
In a four-week trial in Alzheimer’s disease patients designed primarily to evaluate the safety and tolerability of AZD1446 when administered with donepezil (the most commonly prescribed Alzheimer’s disease treatment), AZD1446 exhibited a safety and tolerability profile acceptable for further development. As expected with a short dosing period and small number of subjects, AZD1446 did not show an effect on surrogate measures of cognition and global function in the study.
In a separate trial designed to explore the effects of a single dose of AZD1446 in healthy volunteers with drug-induced cognitive impairment, pro-cognitive signals were observed on various secondary outcome measures, but neither AZD1446 nor the positive comparator donepezil demonstrated a statistically significant effect on the study’s primary outcome measure. Another trial, designed to evaluate pharmacodynamic effect on brain response in Alzheimer’s disease patients as assessed by electroencephalography (EEG), is ongoing.
Additional information regarding AZD1446 clinical trials is available at http://www.clinicaltrials.gov/ct2/results?term=azd1446
About Alzheimer's disease
The treatment of Alzheimer’s disease is currently dominated by a class of drugs called acetylcholinesterase inhibitors. Acetylcholinesterase inhibitors have limitations in that only about half of Alzheimer’s disease patients who take them show symptomatic improvement, and the drugs do not substantially delay the progressive deterioration and death of cells in the brain that can lead to more severe impairment and debilitation.
A 2007 study conducted by researchers at Johns Hopkins University estimated that over 26 million people worldwide suffer from Alzheimer’s disease. In the United States, Alzheimer’s disease is estimated to affect more than five million people and the number of people age 65 and over afflicted is projected to increase by more than 50 percent to 7.7 million by 2030.
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