Adolor and Glaxo are pushing ahead with Entereg, even though tests were suspended for another bowel disorder after a higher number of heart attacks, bone fractures and abnormal tissue growth was seen in patients taking the med. The drugmakers estimate their treatment could be used in about 400,000 patients recovering from surgery in the hospital, annually. "I think for the patient's sake, I would agree that the benefits marginally overcome the negative," said panel member Robert Levine, a professor in gastroenterology at the State University of New York in Syracuse.
Entereg blocks the negative effects of the powerful opioid painkillers, such as morphine, on bowel motility. Wyeth and Progenics Pharmaceuticals are working on a similar drug, although the FDA earlier this month delayed that review because of the drug's potential for disrupting the heart's electrical system. During today's meeting, in fact, a majority of panel members said they were "concerned" about the long-term cardiovascular risks with Entereg.
Last year, the FDA held up development of the drug after a large one-year study testing the drug for a separate chronic bowel condition found an increased number of patients on the drug had heart attacks, bone fractures and some cancers.
A Glaxo exec described those findings as an anomaly, blaming sicker patients and arguing that a small number of events made the results difficult to interpret. Still, Glaxo proposed an additional study to probe the safety risk signal. The evidence suggests "this is not really just a chance finding," said Michael Proschan, a panel member and statistician based in Maryland, who voted against approval.
In the studies for the surgery use, the FDA found a heart attack rate similar to that of a placebo, but the FDA staffers said no conclusion about long-term risks such as heart attack could be drawn because of limited patient follow-up. Most patients were tracked for a maximum of two weeks. In the earlier study for a different bowel disorder, when a higher number of heart attacks were seen, patients were followed for up to a year.
Panel members were unimpressed by a proposed "risk map," a plan that the FDA asked the company to submit to mitigate potential risks to the drug. It included limiting distribution and educating doctors. "I think the risk map done by the company was done very haphazardly," said Alan Buchman, associate professor in gastroenterology at Northwestern University. Buchman and others worried that once the drug reached the market, surgeons would use it in non-bowel surgeries for which it was not tested.