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Arrowhead Pharmaceuticals presents plozasiran and zodasiran data at AHA 2023

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At the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia, US, Arrowhead Pharmaceuticals unveiled the Phase II clinical data for plozasiran (ARO-APOC3) and zodasiran (ARO-ANG3).

The Phase II SHASTA-2 study showed that plozasiran decreased APOC3 to -79%, triglycerides (TG) to -74%, remnant cholesterol to -65% and increased high-density lipoprotein (HDL)-cholesterol (HDL-C) to 68% at 24 weeks in patients with severe hypertriglyceridemia.

In the Phase II ARCHES-2 study, zodasiran showed reductions of ANGPTL3 up to -71% at week eight, TGs up to 59% at week 16, and low-density lipoprotein (LDL)-C up to -32% at week 16 in patients with mixed dyslipidemia.

Plozasiran is expected to reach sales of $651m by 2030 while zodasiran is expected to reach sales of $399m by 2029, according to GlobalData’s analyst consensus sales forecast.

Plozasiran (ARO-APOC3) is an antisense oligonucleotide (ASO) and zodasiran (ARO-ANG3) is a small interfering RNA and are both RNA-based therapies that target specific genes involved in lipid metabolism such as angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C3 (APOC3).

ANGPTL3 is a protein that regulates lipid metabolism, and inhibiting this protein has been shown to reduce TG levels.

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By GlobalData

Arrowhead’s zodasiran (ARO-ANG3) is being investigated by Arrowhead Pharmaceuticals for the treatment of homozygous familial hypercholesterolemia (HoFH), with plans for Phase III clinical trials.

ARO-ANG3 is forecast to launch in 2026. In March 2023, Arrowhead Pharmaceuticals announced that the FDA had granted fast-track designation to ARO-APOC3 for reducing triglycerides in adult patients with familial chylomicronemia syndrome (FCS).

ARO-APOC3 is being investigated in a Phase III clinical study in patients with FCS and is forecast to launch in 2026.

According to key opinion leaders interviewed by GlobalData, there is an unmet need for drugs that treat severe genetic disorders, including FCS and familial FH.

Currently, there are no FDA-approved therapies to treat FCS. Therefore, there is a critical unmet need for new FCS treatments that effectively lower triglyceride levels and prevent the complications associated with this disease.

If approved, plozasiran and zodasiran will offer hope to dyslipidemia patients. However, drug developers will need to carefully consider how they price their medications and which patients they will initially target in order to successfully penetrate the market.