Arrowhead Pharmaceuticals Initiates Phase 1/2a Study of ARO-DIMER-PA

The First Dual Functional RNAi Therapeutic for the Treatment of Mixed Hyperlipidemia

Jan. 28, 2026 at 8:31am

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Arrowhead Pharmaceuticals has dosed the first subjects in a Phase 1/2a clinical trial of ARO-DIMER-PA, its investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for atherosclerotic cardiovascular disease (ASCVD) due to mixed hyperlipidemia. ARO-DIMER-PA is designed to silence expression of both proprotein convertase subtilisin kexin 9 (PCSK9) and apolipoprotein C3 (APOC3) genes, making it the first clinical candidate to target two genes simultaneously in one molecule.

Why it matters

Mixed hyperlipidemia is a highly prevalent disorder characterized by elevated levels of both low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs), and is a major risk factor for ASCVD, the leading cause of mortality worldwide. Despite the efficacy of LDL-C-lowering therapies, there remains substantial residual risk in patients with mixed hyperlipidemia. ARO-DIMER-PA has the potential to reduce the risk of ASCVD for people living with mixed hyperlipidemia by targeting both PCSK9 and APOC3, which have substantial clinical validation as important targets for reducing LDL-cholesterol, triglycerides, and total atherogenic lipoproteins.

The details

In preclinical studies, ARO-DIMER-PA potently lowered serum PCSK9 and APOC3, and ameliorated high levels of non-HDL-cholesterol, LDL-cholesterol, and triglycerides in hyperlipidemic nonhuman primates. The initiation of the clinical study for ARO-DIMER-PA is the latest advance in Arrowhead's growing focus on RNAi therapeutics in the cardiometabolic therapeutic area.

  • Arrowhead has dosed the first subjects in the Phase 1/2a clinical trial of ARO-DIMER-PA.

The players

Arrowhead Pharmaceuticals

An American pharmaceutical company that develops medicines that treat intractable diseases by silencing the genes that cause them.

ARO-DIMER-PA

Arrowhead's investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for atherosclerotic cardiovascular disease (ASCVD) due to mixed hyperlipidemia.

PCSK9

Proprotein convertase subtilisin kexin 9, a gene that ARO-DIMER-PA is designed to silence expression of.

APOC3

Apolipoprotein C3, a gene that ARO-DIMER-PA is designed to silence expression of.

Chris Anzalone

President and CEO at Arrowhead Pharmaceuticals.

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What they’re saying

“Arrowhead is at the forefront of innovation in the RNAi field, and we're proud of the versatile capabilities of our TRiM™ platform, now including the first-ever clinical candidate that can potentially silence expression of two genes in one RNAi molecule.”

— Chris Anzalone, President and CEO (Arrowhead Pharmaceuticals)

What’s next

The ARO-DIMER-PA-1001 Phase 1/2a study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and effects on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) of single-dose ARO-DIMER-PA (part 1) and multiple doses of ARO-DIMER-PA (part 2) in up to 78 adult subjects with mixed hyperlipidemia.

The takeaway

ARO-DIMER-PA represents an important advancement in the field of RNAi therapeutics, as it is the first clinical candidate designed to silence the expression of two genes simultaneously with a single molecule. If successful, it has the potential to significantly reduce the risk of atherosclerotic cardiovascular disease in patients with mixed hyperlipidemia, an area of high unmet medical need.