Plozasiran is a small interfering RNA (siRNA) therapeutic agent designed to target and reduce the hepatic production of apolipoprotein C-III (APOC3).
APOC3 is a key regulator of triglyceride metabolism, and its inhibition leads to a significant reduction in circulating triglyceride levels.
It has efficacy in managing conditions associated with severe hypertriglyceridemia, such as persistent chylomicronemia and mixed hyperlipidemia, which are linked to increased risks of acute pancreatitis and atherosclerotic cardiovascular disease.
In phase 3 trials, in patients with persistent chylomicronemia who received plozasiran showed a median reduction in fasting triglyceride levels of up to 80% compared to baseline, significantly lowering the incidence of acute pancreatitis.
SHASTA-2 trial, plozasiran achieved dose-dependent reductions in triglyceride levels, with the highest dose resulting in a 57% reduction at 24 weeks.