Bristol-Myers Squibb Company and AstraZeneca announced results from a pre-specified meta-analysis of cardiovascular (CV) safety data from 14 Phase 2b/3 trials in adult patients with type 2 diabetes, which showed that the investigational compound dapagliflozin was not associated with an unacceptable increase in CV risk relative to all comparators pooled in the clinical program. The meta-analysis, presented at the American Heart Association (AHA) Scientific Sessions in Orlando, FL, was conducted in accordance with the U.S. Food and Drug Administration (FDA) guidelines for the assessment of CV safety in new anti-diabetic treatments.
The meta-analysis included 6,228 patients, with 4,287 patients in the dapagliflozin group and 1,941 patients in the control group. The primary endpoint was a composite endpoint of time to first event of CV death, myocardial infarction (MI), stroke or hospitalization for unstable angina. The relative risk between dapagliflozin and the control group, measured by hazard ratio, was 0.67 (98% CI: 0.38, 1.18).
“This comprehensive analysis provides valuable information that can be used to better understand the cardiovascular safety profile of dapagliflozin as a monotherapy or as an add-on therapy to common anti-diabetic treatments,” said Brian Daniels, M.D., senior vice president, Global Development and Medical Affairs, Bristol-Myers Squibb.
“We are pleased that the findings from this meta-analysis support the cardiovascular safety profile of dapagliflozin in adult patients with type 2 diabetes, and we look forward to conducting additional research to continue to expand our understanding of dapagliflozin,” said Howard Hutchinson, M.D., chief medical officer, AstraZeneca.
Dapagliflozin, an inhibitor of SGLT2, a target in the kidney, is under joint development by Bristol-Myers Squibb and AstraZeneca. Dapagliflozin, as an adjunct to diet and exercise, is being investigated to evaluate its safety and its efficacy on blood sugar levels (glycosylated hemoglobin levels, or HbA1c) in adults with type 2 diabetes, for use as a monotherapy and in combination with other anti-diabetic agents. A New Drug Application (NDA) for dapagliflozin was accepted for review by the FDA in March 2011. The FDA recently extended the Prescription Drug User Fee Act (PDUFA) date by three months, setting the new goal date at January 28, 2012.
If dapagliflozin is approved, Bristol-Myers Squibb and AstraZeneca plan to conduct a large, post-marketing, randomized, controlled clinical CV outcomes study of the drug in patients with type 2 diabetes which will provide data on the long-term safety profile of dapagliflozin and examine whether or not the drug may provide a cardio-protective effect.
Date: November 16, 2011
Source: Bristol-Myers Squibb Company