Arrowhead Pharmaceuticals has dosed the first participant in the randomised, multicentre Phase III YOSEMITE trial of the investigational RNA interference (RNAi) therapeutic, zodasiran, under development for treating homozygous familial hypercholesterolemia (HoFH).
This rare genetic condition leads to extremely high levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of cardiovascular disease from an early age.
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Formerly known as ARO-ANG3, the therapy is the fourth RNAi-based candidate from the company to progress to late-stage pivotal trials, following plozasiran, fazirsiran (licensed to Takeda), and olpasiran (licensed to Amgen).
The placebo-controlled study is aimed at assessing the safety and efficacy of zodasiran in adults and adolescents with HoFH on maximally tolerated lipid-lowering therapy.
Nearly 60 participants over the age of 12 years will be randomised in a 2:1 ratio and will be given either the four doses of 200mg of the therapy or a placebo once every three months.
The percentage change from baseline to month 12 in fasting LDL-C levels is the primary endpoint of the trial.
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By GlobalDataFollowing this period, eligible subjects will have the option to join an open-label extension of the study.
According to the company, earlier clinical trials indicated that zodasiran was related to dose-dependent decreases in triglycerides, triglyceride-rich lipoprotein remnants, and total atherogenic lipoproteins in individuals with both homozygous and heterozygous familial hypercholesterolemia, as well as mixed hyperlipidaemia.
Zodasiran’s safety profile was also found to be favourable, with no drug-related serious adverse events, discontinuations, or mortalities reported in the Phase II GATEWAY trial.
Arrowhead Pharmaceuticals research and development (R&D) head and chief medical officer James Hamilton said: “Patients living with HoFH are difficult to adequately treat and have a very high risk of developing atherosclerotic cardiovascular disease due to severely elevated LDL-C, often exceeding 500mg/dL.
“In Phase II clinical studies, patients with HoFH receiving zodasiran achieved reductions from baseline in LDL-C, ApoB, non-HDL-C, and triglycerides, supporting its potential therapeutic role for the treatment of HoFH patients.”
Last month, Arrowhead dosed the first participant in the Phase I/IIa AROALK7-1001 trial of ARO-ALK7, an investigational RNA interference therapeutic for obesity.
