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Top-Line Results From Phase 3 Trial of Succinobucol Show Reduction in Hemoglobin A<sub>1c</sub> Compared to Placebo
"We are pleased that the ANDES trial met the primary endpoint and showed a dose response in reducing A1c. Based on the results of this successful trial, AtheroGenics intends to rapidly move forward with development of AGI-1067," said Russell M. Medford, M.D., Ph.D., President and Chief Executive Officer of AtheroGenics. "We believe that AGI-1067, through its unique mechanism of action, could become the first diabetes treatment with demonstrated cardiovascular safety, and with the potential to reduce cardiovascular hard events including cardiovascular death, heart attack and stroke, as reported from the 6,144 patient Phase 3 ARISE trial, which concluded in 2007."
ANDES, an international, double-blind trial, showed a dose-dependent, statistically significant drop in A1c of 0.6% and 0.4% in the 150mg and 75mg arms, respectively, at 6 months, compared to baseline (p In the trial, a regional variation was observed in the placebo arm. Eastern Europe showed a significant decrease of 0.5% for A1c in the placebo arm versus baseline. The other study regions showed an increase of 0.1% in A1c in the placebo arm versus baseline. Importantly, A1c reductions in both AGI-1067 treatment arms were similar across all of the regions in the study. The study analysis plan was prospectively designed to detect and analyze the effect of regional differences. AtheroGenics will continue to analyze the trial data, including the impact of regional differences.
Based on a preliminary review of the safety data, AGI-1067 was well-tolerated and was not associated with weight gain or hypoglycemia in either of the treatment groups. There was no difference in discontinuations between the groups receiving active drug and placebo. One patient in the 150mg arm and two patients in the 75mg arm had unexplained liver enzyme elevations of greater than five times the upper limit of normal. The liver enzyme elevations either have resolved or are resolving.
The Company also announced today that it has developed a patient identification tool to screen for the small number of patients who are potentially at risk for adverse hepatic effects that have been observed during treatment with AGI-1067. The tool has performed well at identifying at-risk diabetes patients across all doses used in the ARISE and ANDES trials.
"We are excited about the advances we have made to date with the patient identification tool for AGI-1067," commented Alexander Fleming, M.D., Acting Chief Medical Officer. "We plan to incorporate this tool into the next AGI-1067 Phase 3 trial."
The data represent findings from a multinational, double-blind, placebo-controlled, dose-finding study of patients with Type 2 diabetes (ages 18-75) who were on one or no other oral anti-diabetes therapies and whose A1c level was greater than or equal to 7.5% and less than or equal to 10.5% and completed the study. A total of 999 patients were enrolled in the ANDES study, including 887 in the current three-arm protocol. The trial included approximately 150 clinical sites in the United States, South Africa, India and Eastern Europe.
AGI-1067 is a novel oral drug candidate with demonstrated anti-inflammatory and antioxidant properties. AGI-1067 works by selectively inhibiting signaling pathways that are activated in response to oxidative stress and pro-inflammatory stimuli. Oxidative stress and inflammation have been implicated as playing a key role in the pathogenesis of insulin resistance and diabetes.
About Type 2 Diabetes
Diabetes (diabetes mellitus) is a chronic disease in which the body does not produce enough insulin (insulin deficiency), or the cells ignore the insulin (insulin resistance). Insulin is a hormone that is needed to convert sugar and starches (carbohydrates) into energy needed for daily life. The cause of diabetes continues to be investigated, and both genetic and environmental factors such as obesity and lack of exercise appear to play a role. The disease may lead to blindness, heart disease, stroke, kidney failure, amputations and nerve damage. Type 2 (adult onset) diabetes accounts for approximately 90 to 95 percent of all diabetes. This equates to roughly 221 million people with type 2 diabetes globally, and 24 million people in the U.S. alone. The American Diabetes Association recommends an A1c measurement of less than 7% for most people with Type 2 diabetes. A1c is a measurement of a person's average blood glucose level over a two-to-three month period and is considered an important marker of long-term glucose control.