ARO-DIMER-PA

ARO-DIMER-PA is a dual-functional RNA interference (RNAi) therapeutic developed by Arrowhead Pharmaceuticals. It is designed as a single, chemically linked small interfering RNA (siRNA) molecule that simultaneously silences the expression of two genes in hepatocytes: **proprotein convertase subtilisin kexin 9 (PCSK9)** and **apolipoprotein C3 (APOC3)**. By targeting both PCSK9 (to lower LDL cholesterol) and APOC3 (to lower triglycerides), ARO-DIMER-PA offers a "two-for-one" approach to address mixed hyperlipidemia, a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Mechanistically, PCSK9 regulates LDL receptor recycling, influencing plasma LDL cholesterol, while APOC3 suppresses lipoprotein lipase activity, raising triglyceride levels. In preclinical nonhuman primate models, a single subcutaneous dose of ARO-DIMER-PA led to approximately 50% reductions in both LDL cholesterol and triglycerides, with sustained effect for nearly two months and a highly liver-specific distribution. These findings suggest potential advantages over single-target lipid-lowering agents, such as longer dosing intervals and greater efficacy. ARO-DIMER-PA uses Arrowhead's proprietary Targeted RNAi Molecule (TRiM) platform for liver-directed delivery via GalNAc conjugation. The therapy is advancing toward Phase 1/2a clinical trials for mixed hyperlipidemia and ASCVD[1][2][4][5][6][7][9][10].

Brand names

ARO-DIMER-PA

Other names

ARO-DIMER-PA