Long-Acting Insulins Win FDA Panel Support

SILVER SPRING, Md. -- An FDA advisory committee voted 8-4 Thursday in favor of approval of a new ultra-long-acting insulin for type 1 and type 2 diabetes.
But the Endocrinologic and Metabolic Drugs Advisory Committee also voted unanimously (12-0) in support of a cardiovascular outcomes trial for the product's two formulations, insulin degludec (Tresiba) and insulin degludec/aspart, (Ryzodeg), due to a potential signal in a meta-analysis of major trials conducted thus far.
The majority of panelists who voted in favor of approving the drug said such a trial could be done post marketing.
"I think this agent has advantages over what's currently available," said panelist Ellen Seely, MD, of Harvard University in Boston. "Both insulin glargine (Lantus) and insulin detemir (Levemir) were supposed to be 24-hour insulins but fell short of that. We've spent a long time searching for an insulin that would last 24 hours."
Thomas Weber, MD, of Duke University Medical Center, said he was impressed by the pharmacokinetics and that a true ability to dose just once a day, at any time, would help improve adherence among patients.
Yet some panelists said that the benefits of the drug were not overwhelming and expressed strong concerns over cardiovascular risks that may not outweigh any advantages.
Brendan Everett, MD, MPH, a cardiologist at Brigham & Women's Hospital in Boston, voted against approval, noting that diabetics already have a substantial burden of heart disease tied to high morbidity and mortality.
He cited current "experience with other anti-diabetic medications that have adverse cardiovascular risk profile but are widely used. As a result, we've put patients at risk for adverse outcomes."
"I don't know that what we've seen [in terms of a cardiovascular signal] is real," he added, "but I have enough concerns about it that I would want to know the answer before a large number of patients with diabetes take this medication."
Erica Brittain, PhD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., who also cast a "No" vote, said she doesn't "feel comfortable exposing millions of patients to a drug when there is this much concern about the cardiovascular risks."
Robert Smith, MD, of Brown University in East Providence, R.I., and Marvin Konstam, MD, of Tufts Medical Center in Boston, cast the other dissenting votes.
In a separate vote on whether a cardiovascular outcomes trial is necessary, Brittain said her "Yes" vote was the "easiest vote I've had since I've been on this committee."
William Hiatt, MD, of the University of Colorado in Aurora, said he voted in favor of such a trial because the mechanism linking the insulin to heart problems "is completely unclear."
"Understanding what might be at play may be important in addition to simply counting events," Hiatt said.
Panelists' interpretations as to whether the insulin was associated with a lower risk of hypoglycemia compared with other insulins were varied. Many felt the risk of hypoglycemia was comparable to other therapies, though some believed there was indeed a signal for reduced hypoglycemic events with both versions of insulin degludec.
In its review of 16 trials, FDA found a suggestion of an excess risk of cardiovascular events with degludec compared with other insulins. The agency has continued to delay a decision on the company's new drug application, submitted last September.
The FDA was initially supposed to deliver its decision in October. The agency isn't obligated to follow the advice of its advisory committees, but often does.
European regulators gave the product a thumbs up last month.

Fuente: http://www.medpagetoday.com/Washington-Watch/FDAGeneral/35854?utm_source=breaking-news&utm_medium=email&utm_campaign=breaking-news