Applied Therapeutics, Inc. – FDA EIR, May 3, 2024

An FDA inspection was conducted at Applied Therapeutics Inc. in New York, NY, from April 29 to May 3, 2024. This high-priority inspection, requested by CDER and OSI under Compliance Program 7348.810, focused on the company's oversight and quality management of clinical protocol (b)(4) supporting New Drug Application (b)(4). At the inspection's conclusion, a Form FDA-483 was issued to the CEO, highlighting three significant observations. First, source data for 11 subjects in the (b)(4) Portal had been deleted on March 27, 2024, preventing verification of critical efficacy data. Second, discrepancies were found between source and generated datasets for efficacy endpoint assessments after submission of study data to the FDA, indicating data quality issues. Third, the company failed to consistently use or complete signed Rating Change Forms for approximately (b)(4) data change queries, compromising data integrity and audit trails. Beyond these observations, the inspection report detailed inadequate sponsor oversight of outsourced services, particularly concerning data management, which led to significant data quality and reliability problems. Issues included insufficient quality control and assurance activities, unattributable patient data, deviations from data collection protocols, and challenges in documenting adjudicated scores. Concerns were also raised about unblinded personnel's involvement in subsequent changes to efficacy endpoints without clear supporting documentation. Applied Therapeutics Inc. is required to address these deficiencies and implement comprehensive corrective actions to ensure robust data integrity, enhance oversight of outsourced activities, and adhere to regulatory standards.