GSK/Adolor's Entereg Eligible For Approval, But Lacks Proper Risk Management Plan, Advisory Panel Says
This article was originally published in The Pink Sheet Daily
Executive Summary
Entereg NDA has Feb. 10 user fee date for gastrointestinal recovery after bowel resection surgery.
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GlaxoSmithKline/Adolor's Entereg (alvimopan) benefits outweigh risks for treatment after bowel resection surgery, but its risk management plan is inadequate, FDA's Gastrointestinal Drugs Advisory Committee has found. During a Jan. 23 meeting, panel members expressed concern that the plan lacks clear definitions and means for patient follow-up, as well as guidelines for restricting off-label use. "The RiskMAP done by the company was done haphazardly," Acting Committee Chair Alan Buchman, Northwestern University, said. "It's short on specifics." In its briefing materials, FDA indicated an effective risk map could assuage the agency's concerns about Entereg's safety, particularly cardiovascular risk. But the agency noted the sponsors' proposal to limit alvimopan use to inpatient hospital facilities poses challenges. Overall, the panel felt alvimopan demonstrates a positive risk-benefit profile for treatment of postoperative ileus. The committee concluded that efficacy results from POI studies were clinically meaningful. Panel members were concerned, however, about safety signals observed in a long-term study in opioid bowel dysfunction. Based on the observance of cardiovascular events, neoplasms and fractures, the committee voted 8-6, with one abstention, that events observed in the OBD population pose a concerning risk for alvimopan use in postoperative ileus. Temporary member Douglas Rosing, National Institutes of Health, was one of six members in the minority. "There is no evidence in the short-term study that there is any cardiovascular risk at all [for alvimopan]," he said prior to the vote. The panel narrowly supported approval of the application, which has so far received two "approvable" letters (1 (Also see "Entereg RiskMAP’s Ability To Prevent Heart Attacks Gets Advisory Panel Review" - Pink Sheet, 22 Jan, 2008.)). Nine committee members voted that Entereg's benefits outweigh the drug's risk for short-term use, while six disagreed. The sponsors' NDA for acceleration of upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis has a Feb.10 user fee date. - Carlene Olsen ([email protected]) |