PK/PD modeling of FXI antisense oligonucleotides to bridge the dose-FXI activity relation from healthy volunteers to end-stage renal disease patients.

ABSTRACT: IONIS-FXI_RX (BAY2306001) is an antisense oligonucleotide that inhibits the synthesis of coagulation factor XI (FXI) and has been investigated in healthy volunteers and patients with end-stage renal disease (ESRD). FXI-LICA (BAY2976217) shares the same RNA sequence as IONIS-FXI_RX but contains a GalNAc-conjugation that facilitates asialoglycoprotein receptor (ASGPR)-mediated uptake into hepatocytes. FXI-LICA has been studied in healthy volunteers and is currently investigated in patients with ESRD on hemodialysis. We present a model-informed bridging approach that facilitates the extrapolation of the dose-exposure-FXI relationship from IONIS-FXI_RX to FXI-LICA in patients with ESRD and, thus, supports the selection of FX-LICA doses being investigated in patien

SUBMITTER: Willmann S 

PROVIDER: S-EPMC8376138 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature