Array BioPharma Inc., a biopharmaceutical company focused on the discovery, development and commercialization of targeted small-molecule drugs, has achieved another milestone in collaboration with Amgen, after Amgen reached a pre-defined patient enrollment level in a phase II a clinical trial. Array entered into an agreement with Amgen in December 2009 for the worldwide development of the small-molecule glucokinase activator (GKA) programme, including AMG 151.
The phase II a trial is a randomized, double-blind, placebo-controlled study of AMG 151 in combination with metformin in patients with Type 2 diabetes. The primary endpoint is change in fasting plasma glucose levels from baseline to end of treatment. Amgen continues to advance the trial and seeks to enroll approximately 224 patients.
Under the agreement, Amgen paid an up-front fee of $60 million. Array is also entitled to receive up to approximately $658 million in additional aggregate milestone payments if all clinical and commercialization milestones specified in the agreement for AMG 151 and at least one backup compound are achieved. Array will also receive royalties on sales of any approved drugs developed under the agreement.
According to the Centers for Disease Control, approximately 26 million Americans have diabetes. Current therapies for this progressive disease are insufficient or have unwanted side-effects creating a need for the development of novel therapeutic approaches.
Glucokinase activators, such as AMG 151, represent a promising new class of drugs for the treatment of Type 2 diabetes. Glucokinase is the enzyme that acts as a glucose sensor in the pancreas and liver. The activation of glucokinase lowers 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. In multiple well-established preclinical models of Type 2 diabetes, AMG 151 was highly efficacious in controlling both fasting and non-fasting blood glucose, with rapid onset of effect and maximal efficacy within five to eight once daily doses. In these studies, when combined with existing standard-of-care drugs (metformin, Januvia (sitagliptin) or Actos (pioglitazone), AMG 151 provided additional glucose control, which reached maximal efficacy after five to seven days of once-daily dosing. AMG 151 did not increase body weight, plasma triglycerides or total cholesterol, whether used as monotherapy or in combination with other diabetes drugs.