FDA Denies Approval of New Diabetes Drug dapagliflozin

Earlier this month, the FDA chose not to approve Bristol-Myers Squibb/AstraZeneca’s dapagliflozin, a member of a class of drugs that causes users to excrete excess glucose through their urine (SGLT-2 inhibitors; see Learning Curve in diaTribe #24). This decision was somewhat expected, given that an outside panel of experts (an “advisory committee”) assembled by the FDA in July 2011 believed that the potential risks of the drug currently outweigh its benefits. As a reminder, the experts on such advisory committees recommend approval/non-approval of a new drug based on the available data from clinical trials to date (see our NewNowNext in diaTribe #35). The FDA then considers the votes and discussion from these advisory panels in its decision to approve the drug. Following the official announcement of non-approval earlier this month, Bristol-Myers Squibb/AstraZeneca have remained rather vague about what the FDA is requesting from them before reconsidering the drug’s approval; for now, the companies have only noted that the agency does indeed want to see additional clinical trial data. It seems likely that the FDA is concerned with the potential cancer risk of dapagliflozin, as late-stage trials uncovered possible increases in the risk of bladder cancer (0.3% of men treated with dapagliflozin versus 0.05% with placebo [inactive pill]) and breast cancer (0.4% versus 0.1% of women). In addition, while the advisory committee seemed confident that the increased frequency of urinary tract infections with dapagliflozin (a characteristic of most SGLT-2 inhibitors in development) could be adequately managed with careful monitoring and antibiotics, it is possible the FDA was not as comfortable and wanted to see better risk management strategies prior to approving the drug. –VW