FDA 483 - Applied Therapeutics, Inc. - May 03, 2024

An FDA inspection of Applied Therapeutics, Inc. took place from April 29 to May 3, 2024, revealing significant concerns related to the conduct of a clinical trial protocol. The primary observation cited was the company's failure to ensure the study adhered to its established protocol and investigational plan. Specifically, investigators found that a service provider deleted critical source data from the Q-Global Portal, rendering it unverifiable. Furthermore, substantial discrepancies were identified between the original source data and generated datasets for efficacy endpoints, with error rates reaching up to 36%. These data integrity issues were discovered only after the datasets had already been submitted to the Food and Drug Administration. The inspection also noted a lack of proper documentation for data changes, as required signed Rating Change Forms were not consistently utilized for numerous updates, contrary to the company's own standard operating procedures. These observations underscore a need for improved oversight in clinical data management and adherence to internal and regulatory standards for clinical trials. Applied Therapeutics, Inc. is now expected to provide a comprehensive response to the FDA 483, detailing the corrective and preventive actions it plans to implement to address these findings.