Arrowhead Pharmaceuticals has announced interim topline data from a Phase I/IIa clinical trial of ARO-DIMER-PA, the company’s first investigational RNA interference (RNAi) therapeutic dimer 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. 

In participants with mixed hyperlipidemia, ARO-DIMER-PA single doses achieved dose-dependent mean maximal reductions in serum PCSK9 of 72% and APOC3 of 88%. 

Silencing of both the PCSK9 and APOC3 genes led to favourable changes in lipids and lipoproteins including the following mean maximal reductions: 

  • LDL-C reduction of 54% 
  • Triglyceride (TG) reduction of 73% 
  • Non-high density lipoprotein (non-HDL) cholesterol reduction of 61% 
  • Apolipoprotein B (ApoB) reduction of 50% 

“With these interim topline results, Arrowhead’s innovative and proprietary Targeted RNAi Molecule (TRiM) platform has achieved clinical validation of its ability to target and silence two genes simultaneously in one molecule. This represents an important step forward and a first for the field of RNAi therapeutics. We look forward to presenting additional details on this groundbreaking advance at an upcoming medical congress,” said Chris Anzalone, President and CEO at Arrowhead Pharmaceuticals. “This validation potentially expands the number of diseases and patients worldwide that may be helped by Arrowhead’s RNAi therapies.  

“ARO-DIMER-PA also fits well strategically with Arrowhead’s growing focus on cardiometabolic diseases. It is complemented by our existing portfolio, which includes our first commercial product REDEMPLO (plozasiran), now approved in the US, European Union, Canada, Australia, and China for the treatment of familial chylomicronemia syndrome (FCS), and investigational zodasiran, which is currently being studied in the global Phase III YOSEMITE clinical trial in patients with homozygous familial hypercholesterolemia (HoFH).”