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FDA advisors vote against new diabetes drug

logo2c.gifA US Food and Drug Administration (FDA) advisory committee has recommended against the approval of dapagliflozin, a diabetes drug that acts by increasing the body’s excretion of sugar.

The final vote was six in favor and nine against the notion that the efficacy and safety data gathered by Bristol-Myers Squibb and AstraZeneca, the drug’s developers, were enough to support approval of dapagliflozin. The FDA does not always follow the recommendations of its advisory panel, but in a brief released in advance of the 19 July meeting, FDA analysts also expressed concerns about safety signals that had surfaced in clinical trials of the drug.

Those signals included an increased risk of urinary tract infections, as well as possible liver toxicity and a possible rise in the risk of breast and bladder cancer. The committee agreed that larger studies were needed to probe cancer risk, but panelists disagreed over whether those studies were best done before approval or post-marketing.

In remarks following the vote, it was clear all of the panelists wanted to like the drug. Dapagliflozin is the first in a new class of diabetes drugs that inhibit a protein called SGLT2 (sodium glucose co-transporter 2). SGLT2 promotes the reabsorption of glucose into the bloodstream in the kidney; blocking it boosts the amount of sugar that is excreted in the urine. So far, it has been tested only in patients with type 2 diabetes, but some argue that the treatment could be effective against type 1 diabetes as well.

“I would love to see this drug approved,” said Eric Felner, a pediatric endocrinologist at Emory University School of Medicine in Atlanta, who voted against approval at the meeting.


The drug promoted weight loss – in contrast to several other available diabetes therapies, which often cause weight gain – improved blood sugar, and performed well when added to existing therapeutic regimens, he said. “But there’s something about the breast and bladder cancer that bothered me.”

Erica Brittain, a statistician at the National Institutes of Health in Bethesda, Maryland, voted ‘no’ but acknowledged that it was a close call. “I changed my mind about four times in the last ten seconds,” she said.

Several who voted in favor of the drug were also concerned about safety, but believed that those concerns were best addressed using post-marketing studies. Requiring drug developers to do the large studies needed to quell cancer concerns before allowing the drug on the market could ultimately stifle innovation, said committee chair Abraham Thomas, an endocrinologist at the Henry Ford Hospital in Detroit, Michigan. “I don’t think that’s realistic for drug development to do that pre-marketing,” he said.

If the FDA asks companies to do that, “we’re not going to have new therapies,” agreed endocrinologist Ellen Seely of Harvard Medical School in Boston.

Nevertheless, safety is king when it comes to diabetes drugs. The current type 2 diabetes epidemic ensures that a new therapy could be taken by many patients, and safety scandals involving diabetes drugs such as GlaxoSmithKline’s Avandia (rosiglitazone) have heightened concerns in the field.

“I think this drug could be a real advance,” says Robert Henry, an endocrinologist at the University of Calfornia, San Diego who was not on the panel. “But you can never argue against safety.”

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