Arrowhead: Plozasiran achieved mean max reductions of up to 90% in APOC3

Arrowhead Pharmaceuticals presented new Phase 2 clinical data from the ongoing SHASTA-2 and MUIR studies of plozasiran and the ARCHES-2 study of zodasiran at the American Heart Association Scientific Sessions 2023, being held in Philadelphia, PA, on November 11-13, 2023. “The compelling data presented today at AHA support the further development of plozasiran in Phase 3 studies, including in patients with severe hypertriglyceridemia, and potentially in a clinical outcomes trial for patients with increased risk for atherosclerotic cardiovascular disease due to elevated triglyceride rich lipoproteins,” said Christie M. Ballantyne, M.D., Baylor College of Medicine. In the Phase 2 SHASTA-2 study of plozasiran in 226 subjects with SHTG who had baseline triglycerides (TGs) of greater than 500 mg/dL, two doses of 10 mg, 25 mg, or 50 mg of plozasiran once every 12 weeks reduced TGs to near normal levels and achieved TG levels below the risk threshold for acute pancreatitis in over 90% of patients. At 24 weeks, plozasiran durably decreased serum APOC3 to -79%, TGs to -74%, and remnant cholesterol to -63%, while increasing HDL-cholesterol to +68%. In the Phase 2 MUIR study of plozasiran in 353 subjects with mixed dyslipidemia who had fasting TGs between 150-499 mg/dL and either LDL-cholesterol greater than 70 mg/dL or non-HDL-cholesterol greater 100 mg/dL, two doses of 10 mg, 25 mg, or 50 mg of plozasiran once every 12 weeks or once every 24 weeks silenced APOC3 and demonstrated robust reductions in atherogenic lipoproteins. At 24 weeks, plozasiran reduced TGs to -64%, remnant cholesterol to -54%, apolipoprotein B to -19%, and Non-HDL-cholesterol to -27%, while increasing HDL-cholesterol to +51%.