Arrowhead announces results from ARCHES-2 study

Arrowhead announced results from the Phase 2b double blind, randomized ARCHES-2 study of investigational zodasiran in patients with mixed hyperlipidemia. Zodasiran was associated with reductions in triglycerides, triglyceride rich lipoprotein remnants, and total atherogenic lipoproteins, including LDL-C. These data were presented in a late-breaking oral presentation at the European Atherosclerosis Society, or EAS, 92nd Congress and simultaneously published in the New England Journal of Medicine. Zodasiran treatment was associated with dose-dependent placebo adjusted reductions in triglycerides, remnant cholesterol, LDL-C, ApoB, and Non-HDL-C across all dose levels in patients with mixed hyperlipidemia. At week 24, representing trough effect, zodasiran treatment at 50, 100, and 200 mg on day 1 and week 12 was associated with placebo adjusted reductions in triglycerides of -51%, -57%, and -63% respectively. ANPTL3, the genetic target of zodasiran, was reduced compared with placebo by -54%, -70%, and -74%, and remnant cholesterol levels were reduced by -73%, -76%, and -82%, which correlated with changes in triglyceride levels. Changes in other atherogenic lipoprotein parameters were also observed across all three dose levels. At week 24, the following placebo adjusted changes were observed for the 200 mg dose: LDL-C -20%, ApoB -22%; Non-HDL-C -36%. In a subset of patients with baseline liver fat fraction greater than 8%, dose-dependent liver fat reductions, measured by MRI-PDFF, were observed reaching -28% with the 200 mg dose compared with -2% with placebo. Zodasiran demonstrated a favorable safety profile in patients with mixed hyperlipidemia in the ARCHES-2 study. Treatment-emergent adverse events, or TEAEs, were generally balanced between treatment and placebo groups and generally reflected the comorbidities and underlying conditions of the study population. There were no clinically meaningful changes in laboratory safety evaluations, no changes in mean platelet counts, and modest changes in HbA1c.