Pancreatitis Associated With Givosiran: A Real-World Pharmacovigilance Study Based on the FAERS and EudraVigilance...

Givosiran is a small interfering RNA therapy approved for the treatment of acute hepatic porphyria. Although clinical trials have demonstrated its efficacy, pancreatitis-related adverse events (AE) have been reported in postmarketing settings. However, real-world evidence remains limited. This study aimed to evaluate the potential disproportionality signal between givosiran and pancreatitis using pharmacovigilance databases.

A retrospective disproportionality analysis was conducted, utilizing relevant data on givosiran from the Food and Drug Administration AE Reporting System (FAERS) database, independent assessment using EudraVigilance. Signal detection was performed using the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. Time-to-onset (TTO), clinical prioritization, stratified, and descriptive analyses of reported dosage information were also performed.

A total of 89 cases were identified in FAERS and 30 in EudraVigilance. Disproportionality analysis showed positive signals for pancreatitis and related events in both databases. Pancreatitis and acute pancreatitis were classified as designated medical events with moderate clinical priority, with hospitalization reported in more than half of the identified cases. The median TTO was approximately 436 days. Among cases with available onset data, 51.73% occurred after 1 year of treatment. Weibull analysis suggested a random failure pattern. Stratified analysis showed consistent disproportionality across different reporter types. For cases with available dosage information. Among cases with available dosage information, the mean reported dose of givosiran was 180.5 mg (range: 94.5-270.45 mg).

These findings identified disproportionality signals for pancreatitis-related AEs reported with givosiran in both pharmacovigilance databases. The relatively long reported TTO suggests that pancreatitis reports were observed throughout treatment, supporting continued pharmacovigilance monitoring during givosiran therapy. Interpretation should consider the inherent limitations of spontaneous reporting systems. Further studies are warranted to determine whether a causal relationship exists.

This study utilizes real-world data from the FAERS and EudraVigilance databases to investigate the safety signal of pancreatitis in patients treated with Givosiran. Analysis of 89 cases (FAERS) and 30 cases (EudraVigilance) revealed significant safety signals for pancreatitis and increased lipase. With a median time-to-onset of 436.14 days, the findings suggest a need for long-term monitoring of pancreatic enzymes during givosiran therapy.