Advisors to the US Food and Drug rejection have voted against recommending approval of Bristol-Myers Squibb/AstraZeneca's diabetes drug dapagliflozin, but it was a far-from-unanimous rejection.
The agency's Endocrinologic and Metabolic Drugs Advisory Committee voted 9-6 against when asked whether the efficacy and safety data provided substantial evidence to support approval of dapagliflozin. The panel noted the concerns of FDA staffers about possible liver damage and the potential link with breast and bladder cancer.
Dapagliflozin is the first drug in the class of sodium-glucose co-transporter 2 (SGLT2) inhibitors. These drugs are designed to block glucose being absorbed into the bloodstream through the kidneys, allowing more sugar to be excreted with urine.
The New York Times quoted committee member David Capuzzi of Thomas Jefferson University, who voted no, as saying that "while I really liked the concept, we just don’t have enough right now, in my opinion, to ensure safety and efficacy and how to use it". Another panellist who voted no, Erica Brittain, a statistician at the National Institutes of Health, said that “I changed my mind about four times in the last 10 seconds".
Given that many calories are excreted through the urine with SGLT2 inhibitors, data has shown dapagliflozin can result in small weight loss, unlike many other diabetes drugs which cause weight gain. Ellen Seely of the Harvard Medical School and Brigham and Women’s Hospital, who voted yes, noted that "finding anti-diabetic agents that are weight-neutral is going to be a huge advance” but acknowledged that "there is a scare factor to the word ‘cancer’.”
The FDA is not bound to follow the advice of its committees and it would be extremely unusual for it approve a drug after a negative vote. However, the agency, which will make a final decision by October 28, will have noted the closeness of the vote.
Most observers believe that B-MS and AstraZeneca will need to provide more data but the key now is whether the FDA will call for new trials or go along the post-marketing study route. The first option would delay approval of dapagliflozin by years.