Arrowhead Pharmaceuticals has reported initial results from Phase I clinical trials of its RNAi-based cardiometabolic candidates ARO-APOC3 and ARO-ANG3 in patients with hypertriglyceridemia and dyslipidemia.

The AROAPOC31001 study is examining 10mg, 25mg, 50mg and 100mg doses of ARO-APOC3 in up to 63 healthy volunteers, as well as in hypertriglyceridemia and familial chylomicronemia syndrome (FCS) patients.

A separate AROANG1001 trial is assessing 35mg, 100mg, 200mg and 300mg ARO-ANG3 in up to 82 healthy volunteers and dyslipidemia patients.

Both the single and multiple-dose studies are designed to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug candidate.

According to the top-line data, ARO-APOC3 minimised plasma Apolipoprotein C-III (apoC-III), while ARO-ANG3 decreased plasma angiopoietin-like protein 3 (ANGPTL3) in healthy individuals.

“We look forward to sharing a fuller dataset in healthy volunteers later this year.”

Both candidates were observed to reduce triglycerides and did not lead to any serious or severe adverse events.

One dose of 100mg ARO-APOC3 demonstrated a 63% mean maximal reduction of plasma triglycerides and 94% of APOC3 protein in healthy volunteers.

A 200mg dose of ARO-ANG3 also demonstrated 66% mean maximal reduction of plasma triglycerides and 79% of ANGPTL3 protein in healthy patients.

Based on the findings, Arrowhead said that the long duration of effect of the therapeutics may facilitate dosing intervals of three months or six months.

Arrowhead Pharmaceuticals chief operating officer and R&D head Bruce Given said: “We look forward to sharing a fuller dataset, including a broader set of lipid parameters and full-time course from the single ascending dose portions of the ARO-APOC3 and ARO-ANG3 Phase I studies in healthy volunteers later this year and the multiple ascending dose portions in various patient populations as data mature.”

The initial data has been presented at The Global Summit on Cardiology and Heart Diseases in Dubai, UAE.

Arrowhead also announced preclinical results of the RNAi candidates.

ARO-ANG3 was found to decrease triglycerides and LDL-C in LDL receptor knockout mice, while improving steatosis and insulin sensitivity in diet-induced obese mice.