FDA CRL - Durect Corp

The FDA issued a Complete Response letter to DURECT Corporation for its New Drug Application (NDA 204803) for POSIMIR (bupivacaine extended-release solution), initially submitted on April 12, 2013. The agency determined that the application could not be approved in its current form due to insufficient information demonstrating the safety of POSIMIR, as required under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The primary safety concerns identified were an inadequately characterized risk profile for SABER-bupivacaine. Specifically, the FDA noted insufficient data regarding adverse events affecting the shoulder joint and surrounding tissues, an increased incidence of skin-related adverse events such as bruising and hematoma, and a substantially higher occurrence of neurologically related adverse events like dizziness and headache. To resolve these issues, DURECT Corporation is required to conduct additional, well-designed, randomized, double-blinded safety studies. These studies must specifically evaluate the risks associated with shoulder joint reactions, skin and underlying tissue reactions, and neurotoxicity, using appropriate comparators. Efficacy data must be collected concurrently to provide clinical context. The FDA also requires a comprehensive safety update and recommends discussion of study designs prior to implementation, reserving comments on labeling until these safety concerns are adequately addressed.