Analysis of adverse event reporting with casimersen: a pharmacovigilance study based on the United States food and...

Casimersen is an antisense oligonucleotide used to treat patients with Duchenne muscular dystrophy (DMD), with mutations amenable to exon 45 skipping. However, real-world safety data are limited.

This study used the Food and Drug Administration Adverse Event Reporting System (FAERS) database to describe post-marketing adverse event reporting patterns associated with casimersen, identify disproportionality signals at the preferred term level, and characterize their onset patterns and affected organ systems.

FAERS reports from 2004 to 2024 involving casimersen were extracted, deduplicated, and coded using the Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analyses were performed using four validated algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM). Signals that met all four criteria were considered statistically significant. Time-to-onset and subgroup analyses according to age and sex were also performed.

Among 21,964,449 FAERS reports, 598 listed casimersen as the primary suspect, predominantly in males (98.5%) and patients aged < 18 years (62.0%). The median time to AE onset was 253 days (range, 101-490 days). Twenty-one System Organ Classes (SOCs) were implicated, including injury, poisoning, procedural complications (n = 377), vascular disorders (n = 85), product issues (n = 80), and social circumstances (n = 13). Using all four algorithms, 30 significantly preferred terms (PTs) were identified, encompassing heterogeneous reporting categories, including clinically oriented terms as well as administration-related, medication use, and non-specific descriptors, such as product dose omission, poor venous access, proteinuria, hematuria, chromaturia, underdose, illness, and infusion-site extravasation.

This study characterized post-marketing adverse event reporting patterns associated with casimersen using FAERS data. By summarizing the preferred term-level reporting distributions, affected organ system categories, and time-to-onset characteristics, the findings provide a descriptive overview of real-world reporting patterns following casimersen use. These results may inform post-marketing pharmacovigilance activities and support hypothesis generation in future studies.