FDA CRL - Gavis Pharmaceuticals, LLC

The FDA issued a Complete Response Letter (CRL) to Marius Pharmaceuticals, LLC for its New Drug Application (NDA 213953) for testosterone undecanoate, filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The primary reason for non-approval is significant concerns regarding the reliability and integrity of the pharmacokinetic (PK) data from the pivotal MRS-TU-2019EXT efficacy and safety trial. During Agency inspections of clinical sites 104 and 107, critical issues were identified, including paradoxically high plasma testosterone concentrations compared to serum, and a severe lack of documentation for PK blood sample processing and handling. This widespread absence of verifiable procedures compromises the overall trustworthiness of the entire study's PK data. Consequently, the FDA could not conclude that the trial provided substantial evidence of effectiveness, as key secondary peak concentration (Cmax) endpoints were not met when all data were included.

To resolve these deficiencies, Marius Pharmaceuticals must conduct a new Phase 3 efficacy and safety trial. This new study requires robust documentation for all PK sample collection, handling, processing, and storage to ensure data reliability. The FDA also recommends measuring testosterone concentrations in both plasma and serum if different sample types are used for dose titration and labeling. Additionally, a comprehensive safety update and resubmission of the proprietary name (Kyzatrex) are required upon addressing all identified issues.