Real-world safety of voretigene neparvovec: a disproportionality analysis for signal detection using the FAERS...

This study aims to evaluate the post-marketing safety profile of voretigene neparvovec using a large spontaneous reporting database. This is a. retrospective pharmacovigilance disproportionality study. Adverse event (AE) reports for voretigene neparvovec were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), Q1 2019-Q1 2025. Disproportionality was assessed using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Signals were summarized at the System Organ Class (SOC) and Preferred Term (PT) levels. A total of 128 AE reports were included. The median patient age was 18 years, with adolescents and young adults comprising the majority. The primary sources of reports were physicians (44.53%) and consumers (43.75%), with intraocular injection being the most frequently reported route of administration (25.00%). Signal analysis revealed that ocular disorders had the highest number of reports and the most prominent signal strength (e.g., retinal degeneration: ROR = 3742.02, IC025 = 6.93; retinal depigmentation: ROR = 8865.67, IC025 = 8.37). Other significant signals included vitreous floaters (ROR = 1497.43, IC025 = 5.43) and elevated intraocular pressure (ROR = 473.10, IC025 = 4.37). In contrast, systemic events such as headache and ocular pain showed weaker signals that did not exceed the statistical significance threshold. In real-world use, voretigene neparvovec is mainly associated with ocular AEs linked to surgical delivery and local inflammatory responses, notably structural retinal changes and intraocular pressure elevations. These findings support careful preoperative assessment, optimized perioperative technique, and close postoperative monitoring. FAERS-based signals indicate association rather than causality and should be interpreted alongside prospective data. Clinical trial number is not applicable.