The FINANCIAL — June 27, 2011 – San Diego, CA – Bristol-Myers Squibb Company and AstraZeneca today announced results from two 24-week Phase 3 clinical studies examining the investigational compound dapagliflozin at 5 mg or 10 mg (clinical trial dose) plus metformin extended-release (XR).
In previously-untreated adults with type 2 diabetes who had high baseline blood sugar levels (glycosylated hemoglobin levels or HbA1c) of up to 12% (mean baseline of 9%), the studies showed that dapagliflozin plus metformin XR significantly reduced blood sugar levels compared to dapagliflozin or metformin XR alone plus placebo. There were no major hypoglycemia-related events in the studies. Minor hypoglycemia was observed more frequently in the combination arm than for either agent alone. The results of the two studies were presented at the 71st American Diabetes Association (ADA) Scientific Sessions in San Diego, CA.
The studies showed that dapagliflozin in combination with metformin XR improved morning blood sugar (fasting plasma glucose, or FPG), had a higher proportion of patients achieving a therapeutic glycemic response of HbA1c < 7% and improved weight reduction compared to dapagliflozin or metformin XR alone.
In addition, the suggested clinical dose of dapagliflozin 10 mg was non-inferior compared to metformin XR in reducing blood sugar levels and was statistically superior to metformin XR in reducing morning blood sugar and weight.
Signs, symptoms and other reports suggestive of genital infections were more common in the dapagliflozin treatment groups in both studies, while signs, symptoms and other reports suggestive of urinary tract infections were more common in the dapagliflozin treatment groups in the 10 mg study. These events were proactively monitored, were generally mild to moderate in intensity and rarely led to study discontinuation, with most patients responding to standard treatment.
“These studies focused on type 2 diabetes patients with high baseline blood sugar levels who may benefit from a combination treatment as initial therapy to help improve blood sugar levels,” said Alexander V. Murray, MD, Medical Director of Research, PharmQuest, a principal investigator of the study. “These studies showed that dapagliflozin as an initial combination therapy with metformin XR helped manage blood sugar levels and other measures of glycemic control in adults who previously had not been treated for type 2 diabetes.”
A New Drug Application (NDA) for dapagliflozin was accepted for review by the U.S. Food and Drug Administration (FDA) in March 2011 with a Prescription Drug User Fee Act (PDUFA) date set for October 28, 2011. In addition, a Marketing Authorisation Application (MAA) was validated by the European Medicines Agency (EMA) in January 2011. If approved, dapagliflozin — an inhibitor of SGLT2, a target in the kidney — would potentially be the first in a new class of insulin-independent, oral type 2 diabetes agents.