PASADENA, Calif. — September 15, 2026

Arrowhead Pharmaceuticals, Inc. announced interim topline clinical data from the Phase 1/2a ARODIMER-PA-1001 study evaluating ARO-DIMER-PA, an investigational dual-functional RNA interference (RNAi) therapeutic for atherosclerotic cardiovascular disease associated with mixed hyperlipidemia. The candidate is designed to silence PCSK9 and APOC3 genes simultaneously with a single RNAi molecule, representing the first clinical candidate in Arrowhead’s pipeline specifically developed for dual-gene silencing. In participants with mixed hyperlipidemia, single-dose administration produced mean maximal reductions of 72% in serum PCSK9 and 88% in APOC3, accompanied by reductions in several atherogenic lipid parameters. Mean maximal reductions included 54% in LDL-C, 73% in triglycerides, 61% in non-HDL cholesterol and 50% in apolipoprotein B (ApoB). Arrowhead said additional results from the ongoing program will be submitted for presentation at an upcoming medical congress..

Dual RNAi Approach Targets Multiple Lipid Abnormalities

ARO-DIMER-PA is designed to address multiple components of mixed hyperlipidemia through simultaneous PCSK9 and APOC3 silencing in hepatocytes. PCSK9 inhibition can reduce LDL-C, while APOC3 inhibition is intended to affect triglycerides and triglyceride-rich lipoprotein remnants. The combined mechanism therefore provides a strategy for addressing both LDL-C and triglyceride-related lipid abnormalities with one RNAi molecule, rather than focusing on LDL-C alone. Arrowhead reported dose-dependent gene silencing in the interim single-dose analysis, with corresponding favorable changes across LDL-C, triglycerides, non-HDL cholesterol and ApoB. The company highlighted the potential clinical relevance of ApoB and LDL-C reductions, while noting that the current findings are early-stage clinical data and that longer-term studies will be needed to determine whether biomarker improvements translate into cardiovascular outcomes. The approach could broaden the application of RNAi-based medicines within cardiometabolic disease as Arrowhead continues expanding its targeted RNAi pipeline.

Phase 1/2a Program Continues Safety and Multiple-Dose Evaluation

The ARODIMER-PA-1001 study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of ARO-DIMER-PA in adults with mixed hyperlipidemia. The placebo-controlled dose-escalation study is designed to enroll up to 78 participants, with a single-dose evaluation followed by a multiple-dose component. Single-dose escalation has been completed through 400 mg, while the multiple-dose portion remains ongoing to further assess safety and tolerability. The most commonly reported treatment-emergent adverse events were injection-site events and headaches, and no drug-related serious adverse events were reported in the interim analysis. The company plans to continue evaluating multiple doses while developing a more complete understanding of the candidate’s durability, pharmacologic activity and safety profile. Additional clinical findings are expected to provide further information on whether the dual-functional RNAi approach can consistently maintain reductions in both PCSK9 and APOC3 over repeated administration.

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Arrowhead Expands Cardiometabolic RNAi Portfolio

The ARO-DIMER-PA program strengthens Arrowhead Pharmaceuticals’ broader focus on cardiometabolic diseases and expands the capabilities demonstrated by its targeted RNAi molecule (TRiM™) platform. The company’s portfolio includes REDEMPLO® (plozasiran), approved in multiple markets for familial chylomicronemia syndrome, and investigational zodasiran, which is being evaluated in the global Phase 3 YOSEMITE study in homozygous familial hypercholesterolemia. ARO-DIMER-PA adds a differentiated dual-target approach that could potentially address multiple atherogenic lipid pathways through a single therapeutic molecule. Arrowhead said the clinical validation of simultaneous PCSK9 and APOC3 silencing could expand the potential applications of its RNAi technology across diseases requiring coordinated modulation of multiple genes. As the ARO-DIMER-PA study advances through multiple-dose evaluation and toward additional clinical presentations, the program represents an important development milestone for Arrowhead’s cardiometabolic pipeline and its broader strategy of applying RNAi to complex disease biology.

Source: Arrowhead Pharmaceuticals press release