FDA CRL - Trevena, Inc.

The FDA issued a Complete Response Letter to Trevena, Inc. regarding its New Drug Application (NDA 210730) for Oliceridine injection, 1 mg/mL, for moderate-to-severe acute pain. The application, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, could not be approved in its current form due to several deficiencies. Clinically, the FDA identified inadequate data to support oliceridine's safety, particularly concerning dose-dependent QT prolongation observed in studies, which lacked sufficient ECG monitoring and characterization. Trevena must conduct a new randomized, active-controlled study with 24-hour Holter monitoring and hourly QT measurements to thoroughly evaluate this effect. Additionally, the safety database was deemed insufficient, requiring at least 350 patients exposed to the highest proposed dose (40 mg) for the longest duration. Nonclinical issues included insufficient characterization of a major human metabolite, TRV0109662, regarding embryo-fetal effects, with concerns about its formation in animal models and reproducibility of analytical assays. Trevena needs to either perform a dedicated embryo-fetal development study for this metabolite or provide validated pharmacokinetic data demonstrating adequate exposure in existing animal studies. Product quality deficiencies involved unvalidated analytical methods for controlling leachables, necessitating validation reports and corresponding stability data. The letter also noted issues with proposed container and carton labeling, including the use of an unacceptable proprietary name ("OLINVO") and inconsistent National Drug Code (NDC) package codes. Trevena is required to address these labeling concerns and resubmit the acceptable proprietary name, "OLINVYK".