Active Ingredient: LUMASIRAN
Lumasiran, a hydroxyacid oxidase 1 (HAO1)-directed GalNAc-conjugated small interfering RNA (GalNAc-siRNA), showed no evidence of QT/QTc interval prolongation across pooled Phase 1/2 concentration-QTc evaluations. Characterized by rapid systemic distribution and clearance within 24 to 48 hours, lumasiran showed a flat exposure-response relationship with no dose-dependent increase in ddQTcF. Model-predicted upper bounds of the 90% confidence intervals for ddQTcF at maximum observed plasma concentrations were strictly below 10 ms. Categorical analyses confirmed zero occurrences of absolute QTcF values above 500 ms or baseline changes exceeding 60 ms, verifying the lack of cardiac electrophysiological liability.
https://doi.org/10.1007/s40262-025-01606-0