Arrowhead Pharmaceuticals Initiates Phase 1/2a Study of ARO-DIMER-PA – the First Dual Functional RNAi Therapeutic for the Treatment of Mixed Hyperlipidemia

- ARO-DIMER-PA is the first clinical candidate designed to silence the expression of two genes with a single RNAi molecule

- 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

- Study initiation further highlights Arrowhead’s innovation and leadership in the delivery of siRNA and the versatility of Arrowhead’s proprietary TRiM^™ technology

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that it has dosed the first subjects in a Phase 1/2a clinical trial of ARO-DIMER-PA, the company’s 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. This represents an important step forward for the field of RNAi therapeutics, as it is the first clinical candidate to target two genes simultaneously in one molecule, enabled by Arrowhead’s innovative and proprietary Targeted RNAi Molecule (TRiM^™) platform.

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, which is the leading cause of mortality worldwide and associated with substantial morbidity and healthcare costs. Despite the efficacy of LDL-C-lowering therapies in reducing ASCVD risk, there remains substantial residual risk in patients with mixed hyperlipidemia.

“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,” said Chris Anzalone, Ph.D., President and CEO at Arrowhead Pharmaceuticals. “ARO-DIMER-PA is designed to silence both the PCSK9 and APOC3 genes, which together have substantial clinical validation as important targets for reducing LDL-cholesterol, triglycerides, and total atherogenic lipoproteins. We see ARO-DIMER-PA as having the potential to reduce the risk of ASCVD for people living with mixed hyperlipidemia, and we are excited to see what this study may reveal about the possibility of creating other dual-functional RNAi molecules for potentially treating complex genetic diseases.”

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 – a portfolio that includes the company’s commercial product REDEMPLO^® (plozasiran), now approved in the U.S., Canada, and China for the treatment of familial chylomicronemia syndrome (FCS), the ongoing Phase 3 study of zodasiran in homozygous familial hypercholesterolemia (HoFH), and ongoing Phase 1/2 studies of investigational ARO-INHBE and ARO-ALK7 being developed as potential treatments for obesity.

Preclinical data on ARO-DIMER-PA were previously presented at the National Lipid Association (NLA) 2025 Annual Scientific Sessions and may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

About ARO-DIMER-PA

ARO-DIMER-PA is a dual-functional RNAi molecule designed to silence expression of both PCSK9 and APOC3 genes in hepatocytes. Prior clinical experience with other investigational and approved agents suggests that PCSK9 and APOC3 inhibition may lead to robust reductions in LDL-C, TGs, triglyceride rich lipoprotein remnants, and total atherogenic lipoproteins.

ARO-DIMER-PA is the first clinical candidate designed to selectively silence the expression of two genes with a single RNAi molecule.

About the ARO-DIMER-PA-1001 Phase 1/2a Study

ARO-DIMER-PA-1001 (NCT07223658) is a Phase 1/2a placebo-controlled dose-escalating study to 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.

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

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Source: Arrowhead Pharmaceuticals, Inc.