Arrowhead Pharmaceuticals has released interim topline data from a Phase I/IIa study of ARO-DIMER-PA, a first-in-class RNA interference (RNAi) dimer designed as a single molecule to simultaneously silence PCSK9 and APOC3, in mixed hyperlipidaemia driven by coexisting LDL-cholesterol and triglyceride elevation.

A single dose produced mean peak reductions of 72% in serum PCSK9 and 88% in APOC3, translating into 54% lower LDL-C, 73% lower triglycerides, 61% lower non-HDL cholesterol, and 50% lower apolipoprotein B, with dose escalation completed to 400 mg and no drug-related serious adverse events, only injection-site reactions and headache.

The asset attacks residual cardiovascular risk that statins and PCSK9 inhibitors leave untouched: APOC3 silencing cuts triglyceride-rich lipoprotein remnants while PCSK9 knockdown deepens LDL lowering, potentially consolidating two mechanisms that today require combining a PCSK9 antibody or siRNA with a triglyceride-targeting agent such as fenofibrate or an APOC3 antisense drug.