Arrowhead’s ARO‑DIMER‑PA Delivers Potent Dual‑Gene Knockdown and Large Lipid Reductions in Phase I/IIa Interim Results

Sep 16•2 min read

The trial will assess the safety

Arrowhead reported interim Phase I/IIa top-line results for ARO‑DIMER‑PA, a dual‑target RNAi therapeutic dimer. In single‑dose cohorts the drug produced mean maximal reductions of 72% (PCSK9) and 88% (APOC3), with corresponding lipid improvements: LDL‑C −54%, TG −73%, non‑HDL‑C −61% and ApoB −50%. The single‑dose escalation reached 400 mg; most common adverse events were injection‑site reactions and headaches, and no drug‑related serious adverse events have been reported. Arrowhead says the results validate its TRiM platform and will share more data at a medical congress.

Arrowhead Pharmaceuticals has reported interim top-line results from its ongoing Phase I/IIa ARODIMER-PA-1001 study of ARO-DIMER-PA, an investigational RNA interference (RNAi) dimer designed to silence two targets simultaneously for the treatment of mixed hyperlipidaemia.

Trial Design

The ARODIMER-PA-1001 trial is evaluating safety, pharmacokinetics, pharmacodynamics and lipid effects in up to 78 adults with mixed hyperlipidaemia. The study includes prespecified single-dose escalation cohorts and planned assessments of repeat dosing to characterize durability, safety and tolerability.

Interim Efficacy Results

In the interim single-dose analysis, ARO-DIMER-PA produced dose-dependent mean maximal reductions of 72% in serum PCSK9 and 88% in APOC3, demonstrating potent dual-gene knockdown from a single molecule. These gene-silencing effects were accompanied by substantial improvements in multiple lipid measures: mean maximal decreases of 54% in LDL‑C, 73% in triglycerides, 61% in non‑HDL‑C and 50% in apolipoprotein B (ApoB).

Safety

The single-dose escalation has progressed through the 400 mg cohort to date. The most frequently reported treatment-emergent adverse events were injection-site reactions and headaches. No serious adverse events considered related to the investigational drug have been reported so far. The trial remains active to further evaluate the safety and tolerability of repeat dosing.

Company Comment and Next Steps

Arrowhead’s president and CEO, Chris Anzalone, said the interim data clinically validate the company’s proprietary Targeted RNAi Molecule (TRiM) platform’s ability to target and silence two genes simultaneously in one molecule. Arrowhead plans to present additional, detailed data at an upcoming medical congress.

Mixed hyperlipidaemia, characterized by concurrent elevations in LDL‑C and triglycerides, is a common contributor to atherosclerotic cardiovascular disease (ASCVD) risk. Separately, in July Arrowhead completed patient enrolment in the global Phase III YOSEMITE study of zodasiran for homozygous familial hypercholesterolaemia (HoFH).