Array BioPharma Reports Positive Results Of Its Oral Glucokinase Activator In Type 2 Diabetes Patients

Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials
Article Date: 11 Aug 2009 - 22:00 PDT

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Array BioPharma Inc. announced yesterday positive top-line data from a Phase 1 clinical trial in patients with Type 2 diabetes with its novel small molecule glucokinase activator (GKA), ARRY-403. The drug met its primary and secondary endpoints of safety, pharmacokinetics and glucose control.

ARRY-403 was evaluated in a Phase 1 single ascending dose study. The study included seven dose cohorts, with a total of 41 patients with Type 2 diabetes receiving either placebo or single doses of ARRY-403 ranging from 25 mg to 400 mg. ARRY-403 was well tolerated at all doses. ARRY-403 was rapidly absorbed, and exposure was dose-dependent. The pharmacokinetic profile is consistent with once daily therapeutic dosing. ARRY-403 provided dose-dependent reduction in glucose excursions in response to a standardized meal as well as reduction in 24-hour fasting blood glucose.

Array is initiating a multiple ascending dose study in patients with Type 2 diabetes to evaluate safety, exposure and glucose control over a 10-day period. The Company plans to report the combined Phase 1 results at an upcoming scientific meeting during the first half of 2010.

"These results are highly encouraging, validating this mechanism-of-action in Type 2 diabetic patients," said Kevin Koch, Ph.D., President and Chief Scientific Officer. "Unlike current therapies, ARRY-403 enhances insulin production from the pancreas while simultaneously regulating glucose metabolism in the liver. Based on the pharmacokinetic and safety profile, coupled with effective glucose control, we believe ARRY-403 has the potential to be a first-line therapy with once-a-day dosing."

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 with unwanted side-effects 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.

About Glucokinase Activation

In normal individuals, the pancreas secretes insulin in response to increased levels of glucose in the blood. Glucokinase (GK) is the enzyme that senses glucose in the pancreas. GK also increases glucose utilization and decreases glucose production in the liver. In patients with Type 2 diabetes, there is a reduction of GK activity in the pancreas and the liver. Activating GK lowers blood glucose levels by enhancing the ability of the pancreas to sense glucose, which leads to increased insulin production. Simultaneously, GKAs increase the net uptake of blood glucose by the liver.

About ARRY-403

In multiple well-established in vivo models of Type 2 diabetes, ARRY-403 is highly efficacious in controlling both fasting and non-fasting blood glucose, with rapid onset of effect and maximal efficacy within 5 to 8 once daily doses. When combined with existing standard-of-care drugs (metformin, sitagliptin, and pioglitazone), ARRY-403 provided additional glucose control, and reached maximal efficacy after 5 to 7 once daily doses. ARRY-403 did not increase body weight, plasma triglycerides or total cholesterol, whether used as monotherapy or in combination with other diabetes drugs.

Source
Array BioPharma

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