Efficacy of Zodasiran, an ANGPTL3-Targeting siRNA, in Reducing Triglycerides and LDL Cholesterol in Mixed Hyperlipidemia
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on October 25th, 2024
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ANGPTL3 is a protein produced by liver cells that plays a role in regulating lipid metabolism by inhibiting lipoprotein lipase and endothelial lipase. Blocking ANGPTL3 can enhance the removal of triglyceride-rich lipoproteins and lower cholesterol levels. Recently, Arrowhead Pharmaceuticals sponsored a study to investigate the potential of zodasiran, a small interfering RNA (siRNA) targeting ANGPTL3, as a treatment for managing hyperlipidemia.
The phase 2 clinical trial included 204 participants diagnosed with mixed hyperlipidemia. The cohort's average fasting triglyceride level was approximately 250 mg/dL, while the mean low-density lipoprotein (LDL) cholesterol level was around 100 mg/dL. Nearly all participants were on lipid-lowering therapies, primarily statins and fibrates. The participants were randomly assigned to receive either a placebo or one of three dose levels of zodasiran: 50 mg, 100 mg, or 200 mg. The treatment was administered subcutaneously at the start of the study and again after 12 weeks. At the 24-week assessment, zodasiran significantly reduced serum triglyceride levels by over 50% and LDL levels by about 15%, with the 200 mg dose showing the greatest efficacy. A previous study published in the Journal of the American Medical Association, and summarized on our website, had found that another siRNA targeting apolipoprotein C3, plozasiran, was effective in managing hypertriglyceridemia at a dose of 25 mg. The researchers noted that future studies can be performed to compare the effectiveness of plozasiran and zodasiran.
The phase 2 clinical trial included 204 participants diagnosed with mixed hyperlipidemia. The cohort's average fasting triglyceride level was approximately 250 mg/dL, while the mean low-density lipoprotein (LDL) cholesterol level was around 100 mg/dL. Nearly all participants were on lipid-lowering therapies, primarily statins and fibrates. The participants were randomly assigned to receive either a placebo or one of three dose levels of zodasiran: 50 mg, 100 mg, or 200 mg. The treatment was administered subcutaneously at the start of the study and again after 12 weeks. At the 24-week assessment, zodasiran significantly reduced serum triglyceride levels by over 50% and LDL levels by about 15%, with the 200 mg dose showing the greatest efficacy. A previous study published in the Journal of the American Medical Association, and summarized on our website, had found that another siRNA targeting apolipoprotein C3, plozasiran, was effective in managing hypertriglyceridemia at a dose of 25 mg. The researchers noted that future studies can be performed to compare the effectiveness of plozasiran and zodasiran.