A phase 1 trial evaluating zodasiran, an angiopoietin-like protein 3 (ANGPTL3)-targeting small interfering RNA, reported no serious treatment-related adverse events in patients receiving background lipid-lowering therapy, according to findings published in Nature Medicine. In this 16-week study, safety was assessed across patients with hyperlipidemia (n=9), familial hypercholesterolemia (FH) (n=17), and moderate-to-severe hypertriglyceridemia (n=6), with a placebo-controlled arm included in the hyperlipidemia cohort.

Zodasiran was administered subcutaneously on days 1 and 29. A 48-week open-label extension was conducted in the FH cohort (n=13), with dosing every 12 weeks. The primary endpoint was treatment-related adverse events. No serious events were observed, and liver enzymes, bilirubin, and glycated hemoglobin (HbA1c) remained unchanged. No treatment discontinuations were reported.

Secondary endpoints included changes in serum ANGPTL3 and triglyceride (TG) levels. At week 16, all cohorts demonstrated reductions, with ANGPTL3 decreasing by up to 85.4% and triglycerides by up to 67.1%. ANGPTL3 reduction was sustained during the extension phase in the FH cohort.

These findings indicate a favorable short-term safety profile and support further clinical evaluation of zodasiran in dyslipidemia.