Arrowhead Pharmaceuticals, Inc. announced results from the Phase 2b double blind, randomized MUIR study of investigational plozasiran (formerly ARO-APOC3) in patients with mixed hyperlipidemia. Treatment with plozasiran in the MUIR study achieved reductions in triglyceride rich lipoproteins, a genetically validated target associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). These data were presented in an oral presentation on May 28, 2024 at the European Atherosclerosis Society (EAS) 92nd Congress and simultaneously published in the New England Journal of Medicine.

Select MUIR Results: By silencing Apolipoprotein C-III (APOC3), plozasiran significantly reduced triglycerides and atherogenic triglyceride rich lipoproteins and increased HDL, across all dose levels at Week 24 in patients with mixed dyslipidemia. At week 24, representing trough effect after 2 quarterly doses, plozasiran treatment was associated with placebo adjusted reductions in triglycerides of -50%, -56%, and -62% (all p<0.001) at the 10, 25, and 50 mg doses, respectively. Fasting triglyceride levels were normalized (achieved levels below 150 mg/dL) in most patients (79-92%) randomized to a treatment arm.

Commensurate reductions in APOC3 of -57%, -73%, and -79%, with strong positive correlations with changes in triglyceride levels were observed. Changes in other atherogenic lipoprotein parameters were also observed. At week 24, for the quarterly doses of 10, 25, and 50 mg, the following placebo adjusted changes were observed: non-HDL-C levels -17%, -18%, and -24%; apoB levels -10%, -13%, and -19%; and remnant cholesterol levels -43%, -49%, and -48% with strong correlations with changes in triglyceride levels.

Safety and Tolerability: Plozasiran demonstrated a favorable safety profile in the MUIR study. The overall rates of occurrence of treatment-emergent adverse events (TEAEs) and discontinuations were similar for plozasiran and placebo throughout the 48 weeks of observation. Observed adverse events generally reflected the comorbidities and underlying conditions of the study population.

TEAEs occurring in 5 or more patients were COVID-19, worsening glycemic control, upper respiratory tract infection, urinary tract infection, headache, and bronchitis. Arrowhead is also presenting data from the SHASTA-2 study of plozasiran and the ARCHES-2 study of zodasiran (formerly ARO-ANG3) at EAS.