BACKGROUND: Gene therapy products are being approved without sufficient clinical evidence to ensure safety at the time of approval. As a result, there is a growing need to monitor post-marketing safety.

OBJECTIVES: To evaluate the safety profile of gene therapy products by examining the adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) by the pharmaceutical industry, healthcare providers, and consumers.

METHODS: A retrospective pharmacovigilance analysis was conducted using FAERS AEs reports. Descriptive statistics were performed. Disproportionality analyses of serious AEs for gene therapeutics compared to the available alternatives for the same proposed indications was calculated using reporting odds ratios (RORs) with 95% confidence intervals (CI) at p < 0.05.

RESULTS: Overall, 57% of the reports were expedited, and 82% submitted by healthcare professionals. Except for voretigene neparvovec, all drugs had a higher percentage of serious AEs than non-serious AEs. In most cases, hospitalization was required. The most common AEs were general disorders and administration site conditions, immune system disorders, and nervous system disorders, which occurred in 20% of the cases. RORs vary depending on the condition, alternative used, and whether it was used alone or in combination with other active ingredients. After approval, lisocabtagene maraleucel, brexucabtagene autoleucel, and idecabtagene vicleucel had a lower percentage of serious AEs. While onasemnogene abeparvovec had a higher percentage of serious adverse events following its approval.

CONCLUSIONS: The use of a gene therapy regimen was often associated with a lower incidence of serious AEs than the standard of care. However, the observed relationship between the gene therapies and the adverse events does not necessarily imply causality. Further investigation is needed to assess the potential causal relationship between the gene therapies and the adverse events.