A U.S. regulatory review of a drug to treat post-operative ileus (POI) found that the subsequent MI rate was similar to that seen with placebo, but the investigators said no conclusion could be drawn because of limited patient follow-up.
The review comes ahead of a Food and Drug Administration advisory panel meeting next Wednesday to consider the drug, Entereg (alvimopan), from Adolor Corp and GlaxoSmithKline.
"In summary, with the available safety data, where multiple approaches were undertaken, the occurrence of serious cardiovascular events appears to be balanced between" patients taking placebo and patients taking Entereg, an FDA staffer wrote, in more than 100 pages of documents released on Friday.
"However, given the limited patient follow-up, complete information is not available, thus no definitive conclusions about cardiovascular safety" can be drawn, the staffer said.
Most patients were followed for a maximum of 2 weeks. In earlier studies looking at Entereg for a different bowel condition, patients were followed for years.
The FDA panel will review the drug for short-term treatment for POI. The FDA typically takes the advice of these advisory panels, made up of outside experts.
Adolor and Glaxo are pushing ahead with development of Entereg for use against POI, despite having to suspend tests of the drug for use against another bowel disorder, opioid-induced bowel dysfunction.
The current application for use against POI had been delayed as the FDA sought more data.
An analysis by FDA staffers said, "The cardiovascular risk emerged only in long-term (6-12 month) testing. However, the short-term trials were not designed to ascertain all cardiovascular events."
The FDA looked at nine safety studies of nearly 4,000 patients, with a 6-day median exposure to the drug.
A lower percentage of patients, 0.5%, died while on Entereg, versus 0.66% on a placebo. The incidence of MIs was similar between the groups.
A smaller number of patients suffered non-fatal serious drug-related adverse events, compared with a placebo.
The difference was mostly due to fewer patients in the Entereg group developing POI. Studies to gauge the drug's effectiveness found it shortened recovery of upper and lower gastrointestinal regularity by about 1 day, and reduced a patient's hospital stay accordingly.
