Hepatic steatosis cohort: effects on exploratory parameters
TG
HEPATIC STEATOSIS
The median TG percentage change from baseline at day 113 was −44.1% for the 200-mg dose compared to an increase of 47.1% for placebo (Extended Data Table The mean (s.d.) LDL-C percentage change from baseline was −34.6% (14.1%) for the 200-mg dose compared to −4.3% (29.3%) for placebo. For ApoB, mean (s.d.) percentage change from baseline at day 113 was −20.5% (15.4%) for the 200-mg dose compared to −0.9% (7.9%) for placebo (Extended Data Table On day 113, the non-HDL-C mean (s.d.) percentage change from baseline was −36.7% (15.0%) for the 200-mg dose compared to 0.2% (14.3%) in the placebo cohort (Extended Data Table Results from MMRM analysis for ANGPTL3, TG, non-HDL-C, VLDL-C, LDL-C, HDL-C, ApoB and other lipids or lipoproteins at day 113 are presented in Extended Data Tables In summary, regardless of study population (HPs or participants with hepatic steatosis), repeat dosing of ARO-ANG3 consistently reduced ANGPTL3 by approximately 80–90%. This reduction was greater than that seen when ARO-ANG3 was given as a single dose. Although the relative change in pharmacodynamic parameters varied by population, and was dependent on baseline concentrations, repeat dosing of ARO-ANG3 consistently provided robust and sustained reductions in key pharmacodynamic parameters (non-HDL-C, VLDL-C, LDL-C and ApoB).