Arrowhead Pharmaceuticals’ hotly anticipated cholesterol disorder drug lowered key lipoproteins that increase the risk of cardiovascular disease in a phase 2 trial, supporting a late-stage program.
The company presented results from the midstage MUIR study of plozasiran at the 92nd European Atherosclerosis Society Congress and published them in The New England Journal of Medicine on Tuesday.
Plozasiran is being tested in patients with mixed hyperlipidemia, a disorder that causes elevated low-density lipoprotein cholesterol (LDL-C) and triglyceride levels. While these patients are typically treated with LDL-C-lowering therapies to reduce the risk of atherosclerotic cardiovascular disease, the risk remains in patients with elevated non-high-density lipoprotein cholesterol (non-HDL-C).
In the MUIR trial, plozasiran reduced atherogenic lipoproteins, such as non-HDL-C, ApoB and remnant cholesterol. After two quarterly doses at Week 24, patients taking the drug had triglyceride reductions of 50%, 56% and 62% at the 10-, 25- and 50-mg doses, respectively. Fasting triglyceride levels normalized in 79% to 92% of patients depending on the treatment arm.
As for safety, Arrowhead’s medicine had a tolerable safety profile with similar levels of treatment-emergent adverse events and discontinuations in the treatment and placebo arms of the study.
Plozasiran, previously known as ARO-APOC3, is an RNA interference therapy that aims to reduce the production of apolipoprotein C-III (APOC3), a known factor in atherosclerosis. The protein is a component of triglyceride-rich lipoproteins and a key regulator of triglyceride metabolism, the company explained. With APOC3 reduced, triglycerides should be reduced and lipids restored to normal levels.
The therapy has been granted orphan-drug and fast-track designations by the FDA and orphan-drug designation in Europe.
Arrowhead previously presented data from the midstage SHASTA-2 study of plozasiran in severe hypertriglyceridemia. The therapy demonstrated improved outcomes at Week 48 and lowered triglycerides and other markers of the condition.
Analysts predict that plozasiran could reach $707 million in sales by 2032 due to its ability to address many forms of dyslipidemia. This group of diseases causes lipids or lipoproteins to be abnormally high or low in the blood, which is a known risk factor for heart disease.
The therapy is already in phase 3 testing for several indications. The MUIR study’s principal investigator, Christie Ballantyne, M.D., from the Baylor College of Medicine, said today’s results reinforce the late-stage program.