Arrowhead Pharmaceuticals has completed patient enrolment in the global Phase III YOSEMITE study of zodasiran, an investigational treatment for homozygous familial hypercholesterolaemia (HoFH).
HoFH is a rare inherited disorder marked by elevated levels of low density lipoprotein-cholesterol (LDL-C) and early onset cardiovascular disease.
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The randomised, double-blind, placebo-controlled and multi-centre study is taking place in several countries.
Arrowhead Pharmaceuticals expects the trial to conclude in mid-2027, after which it plans to seek regulatory approval for zodasiran in various territories, depending on the results.
The study will assess the efficacy and safety of zodasiran in both adolescent and adult patients aged 12 years and above who have genetically or clinically confirmed HoFH and are already receiving the maximum tolerated lipid lowering treatments.
Participants were randomly assigned in a 2:1 ratio to receive 200mg zodasiran or a placebo every three months over four dosing periods.
The primary outcome measure is the percent change in fasting LDL-C from baseline to month 12. Following this period, eligible participants have the option to enter an open-label extension.
Arrowhead Pharmaceuticals chief medical officer and research and development (R&D) head James Hamilton said: “Completing enrolment in the global YOSEMITE Phase III study represents an important milestone in the development of zodasiran for people living with HoFH, a rare disease with limited effective treatment options which carries a very high risk of developing atherosclerotic cardiovascular disease.
“The YOSEMITE Phase III study was initially designed to enrol 60 participants; however, strong global HoFH patient and physician interest led to an increased total of 70 patients enrolled. We believe this speaks to the remaining global unmet need in this population of patients with exceptionally high cardiovascular risk.”
Zodasiran is an investigational RNA interference (RNAi) therapeutic designed to reduce angiopoietin-like protein 3 (ANGPTL3) production.
The product has received orphan drug designation from the US Food and Drug Administration for the treatment of HoFH.
Previous clinical studies have shown dose-dependent reductions in triglycerides and atherogenic lipoproteins in patients with HoFH, heterozygous familial hypercholesterolaemia, and mixed hyperlipidaemia.
The most frequent adverse events reported were nasopharyngitis, Covid-19, upper respiratory tract infection, and dizziness.
Earlier this year, Arrowhead Pharmaceuticals dosed the first participants in its Phase I/IIa clinical trial of ARO-DIMER-PA, an investigational dual functional RNAi therapy, for mixed hyperlipidaemia.
