Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules.

ABSTRACT:

Background

GalNAc-conjugated short interfering RNAs (GalNAc-siRNAs) lack a biologically plausible mechanism for QT/QTc prolongation based on their unique physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties. Nevertheless, regulatory agencies require characterization of QTc effects via either a thorough QT (TQT) study or a concentration-QTc (C-QTc) analysis using early-phase data. This manuscript summarizes platform-level experience across eight GalNAc-siRNAs to assess QTc prolongation risk via C-QTc analysis.

Methods

Time-matched electrocardiogram (ECG) data and plasma concentration data collected from phase 1/2 studies (N = 686), involving healthy subjects and/or patients receiving single ascending doses of study drug or placebo, were us

SUBMITTER: Badri P 

PROVIDER: S-EPMC12881174 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature