FDA Advisory Committee Denies Approval of New Diabetes Drug Dapagliflozin
While the pharmaceutical industry continues to offer new products, it has been over two years since the FDA has approved a diabetes medication with a completely novel drug target. So expectations were high last month when the agency convened its panel of outside experts to discuss Bristol-Myers Squibb/AstraZeneca’s new diabetes medication, dapagliflozin. It’s an SGLT-2 inhibitor, a member of a class of drugs that causes users to urinate out excess glucose (see Learning Curve in diaTribe #24). Though dapagliflozin has been encouraging in effectiveness and its lack of hypoglycemia and weight gain, late-stage trials uncovered possible increases in the risk of bladder cancer (0.3% of men treated with dapagliflozin versus 0.05% with placebo) and breast cancer (0.4% versus 0.1% of women); a single patient on dapagliflozin experienced possible drug-induced liver injury as well, which concerned the FDA. So it wasn’t a surprise that much of the day’s discussion focused on these risks, as we watched from our front-row seats in Silver Springs, MD. Given that the length of drug exposure was not as long as it usually takes a tumor to develop, it wasn’t clear if dapagliflozin was responsible or if some patients may have had underlying cancer before entering the trials. Likewise, with only one patient demonstrating possible drug-induced liver injury, it was difficult for the committee to draw any conclusions. Notably, there was little discussion on the increased risk of urinary tract infections, which many considered one of the biggest drawbacks of SGLT-2 inhibitors – the committee seemed to think infections could be adequately managed with careful monitoring and antibiotics.
In light of the large number of people unable to control their diabetes with current treatments, we were encouraged that many panel members noted the need for new diabetes drugs in clinical practice. But given the possibility of increased risk of life-threatening diseases, the committee concluded in a 9-6 vote that dapagliflozin would not be able to be approved without further data. This follows the very conservative trend at the FDA under the current administration. While the FDA rarely goes against a “no” vote from an advisory committee, the agency is not required to abide by its recommendation. The FDA is expected to make an official decision on dapagliflozin by October 28, 2011. It’s hard to forecast this one, that’s for sure. We here at diaTribe believe that we need more alternatives for people with type 2 diabetes and that the drug should be approved in at least a limited population, with users monitored closely. --VW
