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ASN / Education & Meetings / Kidney Week /
Abstract: TH-PO0843

Real-World Safety Profile of RNA Interference Therapies in Primary Hyperoxaluria: A Pharmacovigilance Study

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Ojha, Vishnu Shankar, Mayo Clinic in Florida, Jacksonville, Florida, United States
  • Biswas, Ratnadeep, New York City Health and Hospitals Jacobi, New York, New York, United States
  • Shashi Kant, Fnu, Cleveland Clinic, Cleveland, Ohio, United States
  • Ashish, Kumar, Nazareth Hospital, Philadelphia, Pennsylvania, United States
  • Wadei, Hani, Mayo Clinic in Florida, Jacksonville, Florida, United States
  • Baker, Lyle Wesley, Mayo Clinic in Florida, Jacksonville, Florida, United States
  • Porter, Ivan E., Mayo Clinic in Florida, Jacksonville, Florida, United States
Background

RNA interference (RNAi) therapies have transformed the management of primary hyperoxaluria (PH); however, real-world safety data remain limited. We evaluated adverse event (AE) patterns, severity, and mortality associated with these therapies using pharmacovigilance data.

Methods

We queried the FDA Adverse Event Reporting System (FAERS) database for AE reported with RNAi: Lumasiran and Nedosiran, between 2021 and March 2026. AEs were categorized according to seriousness and system organ class. Descriptive, mortality, univariate logistic regression (ULR), and multivariate risk analyses (MRA) were performed to identify predictors of serious outcomes and high-risk organ-system involvement.

Results

The mean age was 31.8±22.1 years. Among 302 cases, 239 (79.1%) were serious and 63 (20.9%) were non-serious. Among serious cases, hospitalization occurred in 113 (47.3%), disability in 4 (1.7%), and death in 25 (10.5%). Mortality analysis showed highest mortality with respiratory AEs (29.4%), followed by metabolic/endocrine (17.9%), infectious (12.2%), and cardiovascular system (CVS) AEs (11.5%). ULR analysis (Fig.1) showed infectious AEs were significantly associated with serious outcomes (OR 26.1, p=0.023), hepatic AEs had lower odds of serious outcomes (OR 0.50, p=0.036), and CVS AEs showed a trend toward significance (OR 7.24, p=0.055). MRA (Fig.2) showed combined infectious and CVS AEs had the strongest association with severity, while multi-organ involvement correlated with increased serious outcomes.

Conclusion

Around 8 in 10 reported AEs were serious, with nearly half requiring hospitalization, requiring close monitoring. Early CVS assessment should be considered in patients developing infectious AEs. Multisystem involvement was associated with greater severity and may warrant enhanced monitoring in patients recieving RNAi.

Univariate Analysis

Multivariate Risk Analysis