FDA CRL - UNIV OF CALIFORNIA SAN FRANCISCO

The FDA issued a Complete Response Letter (CRL) to the University of California San Francisco, Department of Radiology and Biomedical Imaging, regarding their New Drug Application (NDA 218353) for Floretyrosine F 18 Injection. The primary reason for non-approval stems from a lack of substantial evidence of effectiveness. The key efficacy study, 18F-TLX101-CDx-203, showed only borderline diagnostic performance with low confidence intervals for sensitivity and specificity, and was considered limited by its single-center design and potential for reference standard bias. Furthermore, confirmatory studies presented design flaws, including potential for unblinding and inconsistent image evaluation. The FDA requires a second adequate and well-controlled efficacy study or robust confirmatory evidence, and suggested considering optimization of the administered dose. Additionally, the application needs a comprehensive safety update, as per 21 CFR 314.50(d)(5)(vi)(b), detailing changes in the safety profile, incorporating new safety data, providing narrative summaries for serious adverse events, and summarizing worldwide experience. Comments on labeling are reserved. The applicant must resubmit a complete response addressing all deficiencies within one year, with a meeting with the FDA recommended to discuss the necessary steps.