Key points discussed include the following:
Top-line data from a single dose of 100 mg of ARO-APOC3 in healthy volunteers demonstrated mean maximal reductions of plasma triglycerides of 63% and APOC3 protein of 94% without serious or severe adverse events
The most common adverse events observed to date, all mild or moderate, have been headache, upper respiratory infection and mild injection site findings
Top-line data from a single dose of 200 mg of ARO-ANG3 in healthy volunteers demonstrated mean maximal reductions of plasma triglycerides of 66% and ANGPTL3 protein of 79% without drug-related serious or severe adverse events
The most common adverse events seen to date, all mild or moderate, have been headache and upper respiratory infection
ARO-ANG3 reduced triglycerides and LDL-C in LDL receptor knockout mice
ARO-ANG3 also ameliorates steatosis and improves insulin sensitivity in diet-induced obese mice
In mouse studies, ANGPTL3 has shown endocrine effects on triglyceride and LDL-C metabolism and apparent autocrine effects on hepatic steatosis and insulin sensitivity
Published research also indicates that APOC3 and ANGPTL3 are strong potential targets for addressing cardiovascular disease
Genetic studies indicate that plasma triglycerides are an independent risk factor for cardiovascular disease
Loss of function mutations of APOC3 or ANGPTL3 are associated with markedly reduced triglycerides and other lipid parameters without reported adverse phenotype
AROAPOC31001 (NCT03783377) is a Phase 1 single and multiple dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ARO-APOC3 in adult healthy volunteers, hypertriglyceridemic patients, and patients with FCS. The study is designed to enroll up to 63 subjects.
The single-ascending dose (SAD) portion of the study included 4 cohorts of 10 adult healthy volunteers with (6 active: 4 placebo). Each SAD subject received a single-dose administration of either placebo or ARO-APOC3 at dose levels of 10, 25, 50, or 100 mg. The multiple-dose portion is designed to include 3 cohorts of patients with severe hypertriglyceridemia and 1 cohort of patients with FCS. The multiple-dose cohorts will receive two monthly doses of ARO-APOC3.