Population pharmacokinetics and exposure-response modeling for evinacumab in homozygous familial hypercholesterolemia.

ABSTRACT: Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). This work characterized the population pharmacokinetics (PK)/pharmacodynamics (PD) of evinacumab using pooled phase III clinical data. Total evinacumab PK were described by a two-compartment model with combined linear and saturable (Michaelis-Menten) elimination, and first-order absorption. At clinically relevant concentrations, plasma drug concentrations were mainly influenced by the linear clearance pathway. Although the maximum target-mediated rate of elimination (V_max ) parameter for the saturable pathway was found to be positively related to baseline ANGPLTL3, vari

SUBMITTER: Pu X 

PROVIDER: S-EPMC8592514 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature