Two different RNA interference approaches that target either apolipoprotein C-III (apoC-III) or angiopoietin-related protein 3 (ANGPTL3) significantly reduce plasma triglyceride levels in patients with mixed hyperlipidaemia. The findings from two phase IIb trials of these agents were presented at the European Atherosclerosis Society Congress.

ApoC-III is a glycoprotein that is present on the surface of all lipoproteins and inhibits lipoprotein lipase, which is involved in the metabolism of triglyceride-rich lipoproteins and their uptake by hepatocytes. Similarly, ANGPTL3 is an endogenous inhibitor of lipoprotein and endothelial lipases and of the hepatic uptake of triglyceride-rich lipoprotein remnants. Plozasiran is a small interfering RNA designed to reduce APOC3 expression in the liver, whereas zodasiran is a small interfering RNA that degrades ANGPTL3 mRNA, thereby inhibiting the hepatic synthesis and secretion of ANGPTL3.