Characteristics of Adverse Events and Clinical Risks of Omaveloxolone Based on FAERS Data

Omaveloxolone, the first approved therapeutic agent for Friedreich ataxia (FRDA), currently has limited real-world safety data available. This study aims to evaluate post-marketing adverse events (AEs) associated with its clinical use by analyzing data from the FDA Adverse Event Reporting System (FAERS). We collected all adverse reaction reports associated with omaveloxolone from the first quarter of 2023 (Q1 2023) to the fourth quarter of 2024 (Q4 2024) in the FAERS database and performed signal detection using four distinct pharmacovigilance methods: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). A total of 9,326,057 AE reports were collected, among which 820 reports were associated with omaveloxolone. All AEs were categorized into 25 System Organ Classes (SOCs) and 67 positive Preferred Terms (PTs). Investigations represented the most frequently reported SOC, followed by gastrointestinal disorders and general disorders and administration site conditions. Hepatic enzyme increased emerged as the most prominent adverse event, demonstrating both high reporting frequency and strong signal intensity, primarily manifesting as elevated ALT and AST levels. Other commonly reported AEs included fatigue, nausea, headache, and blood cholesterol increased. The study also identified several novel potential AEs, such as urinary tract infection, diabetes mellitus, urine odour abnormal, atrial flutter, and urosepsis. Although some of these AEs were reported in relatively low frequencies, their clinical severity and elevated signal strengths suggest that omaveloxolone may potentially affect patients' urinary and endocrine systems, warranting particular attention during clinical administration. In conclusion, while omaveloxolone demonstrates multifaceted benefits in improving neurological function in patients with FRDA, its clinical application necessitates comprehensive evaluation of potential risks, and the development of safe and rational therapeutic strategies is crucial for optimizing treatment outcomes.