GSK/Adolor's Entereg gets approvable letter

US regulators have requested more clinical data on UK drug major GlaxoSmithKline and USA-based Adolor's Entereg (alvimopan). The Food and Drug Administration says that the agent's New Drug Application for the management of postoperative ileus is approvable but has requested 12-month safety data, including analysis of serious cardiovascular events, from study 014, an ongoing safety evaluation in opioid-induced bowel dysfunction, as well as a risk management plan.

The FDA's review of the NDA for POI included the six-month interim analysis of study 014. This analysis was submitted in late September and showed an increase, which was not statistically significant, in the reported incidence of serious CV adverse events in patients on alvimopan relative to placebo. The companies would not disclose the nature of these serious events but noted that they were seen in patients at high risk for CV disease, did not appear to be linked to duration of dosing and were consistent with epidemiological expectations for the subject population. Combined results from all completed studies in the chronic population submitted by GSK to the FDA did not support a conclusion that patients taking alvimopan were at increased risk for serious CV events.

Full 12-month data from study 014 are expected in the second quarter of next year. Analysts were largely agreed that the long-term prospects of the drug and perhaps for the whole alvimopan franchise could be severely damaged if the results are bad. This is the second approvable letter the FDA has given Entereg for this indication. Last year, it requested additional proof of efficacy (Marketletter August 1, 2005). Entereg is a key drug for little Adolor and on the day of the news, November 6, its shares nose-dived 45% to an all-time low of $7.69.