FDA's second review of dapagliflozin from Bristol-Myers Squibb Co. and AstraZeneca plc shows the agency is still on the hunt for any sign of potential CV risk for diabetes candidates - even when they clear the statistical hurdle outlined in 2008 guidance. The Endocrinologic and Metabolic Drugs Advisory Committee, however, appears to have swung back to center in its consideration of risk to benefit ratios.

The first time around, the issue that stymied dapagliflozin was cancer, not cardiovascular risk. In 2011, the panel voted 9-6 against approval, and FDA issued a complete response letter for dapagliflozin, due primarily to an imbalance in breast and bladder cancers, as well as a single case of hepatotoxicity in the clinical program (see BioCentury, July 25, 2011).