Arrowhead Pharmaceuticals (NASDAQ: ARWR) reported Phase 1/2a data Wednesday for its investigational dual-gene RNA interference therapeutic ARO-DIMER-PA, which targets both proprotein convertase subtilisin kexin 9 (PCSK9) and apolipoprotein C3 (APOC3). The results showed mean maximal single-dose reductions of 72% in serum PCSK9 and 88% in APOC3, alongside 54% LDL-C, 73% triglyceride, 61% non-HDL cholesterol and 50% apolipoprotein B reductions.
The phase 1/2a, placebo-controlled, dose-escalating trial enrolled up to 78 adults with mixed hyperlipidemia. A single dose escalation was completed through 400 mg. Arrowhead said the trial represents the "first clinical validation of targeting and silencing two genes simultaneously with one RNAi molecule." The company plans to submit additional results for presentation at an upcoming medical congress.
Safety findings were consistent with the company's existing RNAi portfolio. The most commonly reported treatment-emergent adverse events were injection site events and headaches. No drug-related serious adverse events were reported.
Arrowhead, headquartered in Pasadena, California, already markets REMPLEO (plozasiran) for the treatment of familial chylomicronemia syndrome. The therapy has received regulatory approval in the United States, European Union, Canada, Australia and China. ARO-DIMER-PA is being evaluated in the context of mixed hyperlipidemia and atherosclerotic cardiovascular disease.
