FDA reviewers question CV risk with OIC drugs

FDA reviewers said controlled, long-term safety data "seem critical" to assess the cardiovascular risk of peripherally acting opioid receptor antagonists, though the reviewers cautioned that this is contingent on whether a CV event rate imbalance seen in a Phase III trial for an antagonist "actually represents a true signal" of increased CV risk. The comments came in Entereg alvimopan from Cubist Pharmaceuticals Inc. (NASDAQ:CBST) to treat OIC. The mu opioid receptor ( OPRM1; MOR) antagonist is already approved with a REMS to treat postoperative ileus.

The committee will discuss whether the totality of data, including a potential mechanism, suggests a CV safety signal with opioid receptor antagonists, as well as the feasibility of conducting a CV outcomes trial for OIC in patients with chronic non-cancer pain -- an indication for which efficacy trials are "relatively small in size and treatment duration." FDA is asking the committee to vote on whether the agency should require CV outcomes trials for all or only selected opioid antagonists. The committee also will discuss whether a CV outcomes trial should be required pre- or postapproval or started pre-approval with a plan to submit the NDA when an interim analysis excludes a pre-specified level of risk. ...