Arrowhead Pharmaceuticals Presents Initial Top-Line Clinical Data and Preclinical Data on RNAi Candidates ARO-APOC3 and ARO-ANG3
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.
AROANG1001 (NCT03747224) is a Phase 1 single and multiple dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ARO-ANG3 in adult healthy volunteers and patients with dyslipidemia. The study is designed to enroll up to 82 subjects.
The SAD portion of the study included 4 cohorts of 10 adult healthy volunteers per cohort (6 active: 4 placebo). Each SAD subject received a single-dose administration of either placebo or ARO-ANG3 at dose levels of 35, 100, 200, or 300 mg. The multiple-dose portion is designed to include healthy volunteers, patients with non-alcoholic fatty liver disease (NAFLD), patients on a stable statin treatment regimen with elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides, patients with heterozygous or homozygous familial hypercholesterolemia, and patients with severe hypertriglyceridemia.
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This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.
Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA