Arrowhead Pharma Shares New Phase 2 Data on Plozasiran for Mixed Hyperlipidemia

Arrowhead Pharmaceuticals, Inc. has shared promising results from the Phase 2b MUIR study on their investigational drug plozasiran, formerly known as ARO-APOC3, in patients with mixed hyperlipidemia. The study's findings were presented at the European Atherosclerosis Society's (EAS) 92nd Congress and published in the New England Journal of Medicine.

Plozasiran demonstrated significant reductions in triglyceride-rich lipoproteins—a target linked to increased risk of atherosclerotic cardiovascular disease (ASCVD). Christie M. Ballantyne, M.D., of Baylor College of Medicine, highlighted that plozasiran led to potent and lasting reductions in atherogenic lipoproteins including non-HDL-C, ApoB, and remnant cholesterol. These promising outcomes suggest potential for Phase 3 studies aimed at patients with heightened ASCVD risk.

Bruce Given, M.D., interim chief medical scientist at Arrowhead, expressed optimism about plozasiran's potential in addressing conditions with significant unmet needs such as familial chylomicronemia syndrome, severe hypertriglyceridemia, and mixed hyperlipidemia. He emphasized the importance of further clinical investigations into plozasiran.

Key Findings from the MUIR Study:
Plozasiran works by silencing Apolipoprotein C-III (APOC3), significantly lowering triglycerides and atherogenic lipoproteins, while increasing HDL in patients with mixed dyslipidemia. At Week 24, after two quarterly doses, plozasiran showed placebo-adjusted reductions in triglycerides by -50%, -56%, and -62% at 10, 25, and 50 mg doses, respectively. Most patients saw normalized fasting triglyceride levels below 150 mg/dL. Corresponding reductions in APOC3 were -57%, -73%, and -79%, closely correlating with triglyceride level changes.

Other atherogenic lipoprotein changes included placebo-adjusted reductions in non-HDL-C levels by -17%, -18%, and -24%; ApoB levels by -10%, -13%, and -19%; and remnant cholesterol levels by -43%, -49%, and -48% for the same doses. All changes were strongly correlated with triglyceride level alterations.

Safety and Tolerability:
Plozasiran exhibited a favorable safety profile over the 48-week observation period, with similar rates of treatment-emergent adverse events (TEAEs) and discontinuations as the placebo. Common TEAEs included COVID-19, worsening glycemic control, upper respiratory tract infections, urinary tract infections, headaches, and bronchitis.

Arrowhead is also presenting data from the SHASTA-2 study on plozasiran and the ARCHES-2 study on zodasiran at the EAS Congress.

About MUIR Study:
The MUIR study (NCT04998201) is a Phase 2b double-blind, placebo-controlled clinical trial involving 353 adults with mixed hyperlipidemia. Participants received plozasiran at doses of 10, 25, or 50 mg or a placebo, aiming to evaluate the drug's safety and efficacy. The study focused on adults with fasting triglycerides between 150-499 mg/dL and either LDL-cholesterol above 70 mg/dL or non-HDL-cholesterol above 100 mg/dL.

About Mixed Hyperlipidemia:
Mixed hyperlipidemia, or mixed dyslipidemia, involves elevated levels of LDL cholesterol and triglycerides, contributing to a residual risk for ASCVD despite LDL-C-lowering treatments. Genetic studies support the causal role of triglyceride-rich lipoproteins in ASCVD risk.

About Plozasiran:
Plozasiran is a first-in-class RNA interference (RNAi) therapeutic designed to inhibit APOC3, a key regulator of triglyceride metabolism. The treatment aims to lower APOC3 levels, thereby reducing triglycerides and restoring lipid balance. Plozasiran has shown consistent reductions in triglycerides and atherogenic lipoproteins across several clinical studies in patients with various lipid disorders. It is currently under investigation in multiple Phase 3 clinical trials.

Arrowhead Pharmaceuticals specializes in developing medicines that address intractable diseases through gene silencing via RNA interference.