Zodasiran (ARO-ANG3) significantly reduces TG, ANGPTL3 and triglyceride-rich lipoproteins (TRLs), LDL and total apoB in adult patients with mixed dyslipidaemia, according to results of the Phase 2b ARCHES-2 trial (NCT04832971).
In patients with fasting TG 150-499 mg/dL and LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL, zodasiran 50 mg, 100 mg and 200 mg s.c reduced ANGPTL3 by -54.3%, -69.8% and -73.7% respectively compared to placebo at week 24 (all p<0.0001). This was accompanied by reductions in TG of -51.2%, -56.6% and -63.1% respectively compared to placebo (all p<0.0001).
In addition, remnant cholesterol was reduced by -72.6%, -75.9% and -82.0% respectively, compared to placebo (all p<0.0001), and apoB was reduced by -18.7%, -15.2% and -21.9% respectively compared to placebo (p<0.0001, p<0.05, p<0.0001).
Treatment-related adverse events occurred in 18%-26% of zodasiran-treated patients and 18% of placebo-treated patients. The most common treatment emergent adverse events (TEAEs) across all groups were Covid-19, upper respiratory tract infection and headache. TEAEs leading to drug discontinuation, dose interruptions, or study withdrawal occurred in one placebo-treated patient and one in the zodasiran 100 mg group. There was one death in the placebo group.
“The favourable changes in serum lipids and lipoproteins and safety profile support the potential of ARO-ANG3 to treat residual atherosclerotic cardiovascular disease risk in patients with elevated TRLs not at LDL goal,” concluded the researchers.
Reference
Rosenson RS. ARO-ANG3, an Investigational RNAi Therapeutic, Silences the Expression of ANGPTL3 and Decreases Atherogenic Lipoproteins in Patients With Mixed Dyslipidemia: ARCHES-2 Study Results. Presented at American Heart Association Scientific Sessions 2023 (11-13 November, Philadelphia, USA). PR-APS.P4. Emerging Approaches to Lipid Lowering, Mo3213
