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About ARRY-403 / Glucokinase activation
Glucokinase activators (GKAs) reduce glucose levels via a dual mechanism of action - working in both the pancreas and the liver. Glucokinase (GK) is the Enzyme that senses glucose in the pancreatic beta cells, stimulating insulin release in a glucose-dependent manner. GK also regulates glucose uptake and glucose production in the liver. In diabetic patients, there is a reduction of glucokinase (GK) activity in the pancreas and the liver. The activation of glucokinase lowers glucose levels by enhancing the ability of pancreatic beta cells to sense glucose, in turn increasing the level of insulin that is produced by the pancreas. Simultaneously, GKAs also increase the uptake of glucose in the liver, while reducing the amount of glucose produced by the liver. These combined actions of GKAs result in improved beta cell function and increased insulin sensitivity in the liver.
Preclinical Results
ARRY-403 demonstrated potent, highly glucose-blood-level dependent, control of both fasting and non-fasting glucose concentrations. The data showed that in multiple well-established in vivo models of Type 2 diabetes, ARRY-403 was highly efficacious in controlling both fasting and non-fasting glucose, with rapid onset of effect and maximal efficacy within five to eight days. In combination with existing standard-of-care drugs (metformin, DPP4 inhibitor, or PPAR(gamma) agonist), ARRY-403 provided additional glucose-control, which reached maximal efficacy after five to seven days of once-daily dosing. ARRY-403 showed no adverse increases of body weight, plasma triglycerides or total cholesterol, whether used as monotherapy or in combination.
Future Milestones
Based on these and other results, Array plans to advance ARRY-403 into human clinical studies in the first half of 2009.
About Diabetes
According to the Centers for Disease Control, approximately 24 million (8 percent) Americans have diabetes. Current therapies for this progressive disease are insufficient or inconvenient, creating a need for the development of novel therapeutic approaches. GKAs, such as ARRY-403, represent a promising new class of drugs for the treatment of Type 2 diabetes.
Scientific Posters
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