Arrowhead Pharmaceuticals Announces New Phase 2 Data of Plozasiran Published in JAMA Cardiology and Presented at American College of Cardiology 73rd Annual Scientific Session & Expo

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today presented final data from the double-blind treatment period of its Phase 2 SHASTA-2 study of investigational plozasiran (formerly ARO-APOC3) in patients with severe hypertriglyceridemia (SHTG). Results from the SHASTA-2 study showed dramatic, consistent, and sustained reductions in Apolipoprotein C-III (APOC3) and triglycerides and improvement in multiple atherogenic lipoprotein levels. These data were presented in a late-breaking oral presentation today at the American College of Cardiology 73^rd Annual Scientific Session & Expo (ACC.24) in Atlanta and simultaneously published in the journal JAMA Cardiology.

“Promising results presented today at ACC.24 and simultaneously published in JAMA Cardiology showed that treatment with plozasiran in the SHASTA-2 study led to significant and sustained reductions in triglyceride levels below the threshold associated with elevated risk for pancreatitis. These are important and exciting data as patients with severe hypertriglyceridemia currently have limited treatment options,” said Daniel Gaudet, M.D., Ph.D., Professor of Medicine at Université de Montréal and Principal Investigator for the SHASTA-2 study.

Select SHASTA-2 Results

Treatment with plozasiran led to dose-dependent placebo-adjusted reductions in triglycerides (primary endpoint) of -49% (P < 0.001), -53% (P < 0.001), and -57% (P < 0.001), driven by placebo-adjusted reductions in APOC3 of -68% (P < 0.001), -72% (P < 0.001), and -77% (P < 0.001) at week 24, after receiving two doses of 10 mg, 25 mg, and 50 mg plozasiran, respectively. Mean maximum, non-placebo adjusted reductions from baseline in triglycerides and APOC3 were up to 86% and 90% and typically occurred around week 16 or week 20.

Significant and durable triglyceride and APOC3 reductions persisted to week 48, 36 weeks after the last dose. There was limited interpatient variability in pharmacodynamic response across all plozasiran treatment groups.

Among patients treated with plozasiran, 90.6% achieved a triglyceride level less than 500 mg/dL, the level associated with increased risk of acute pancreatitis, at week 24. In addition, 48.4% of patients achieved normal triglyceride levels of less than 150 mg/dL at week 24.

Subjects treated with plozasiran also showed improvements in multiple atherogenic lipid and lipoprotein levels, including remnant cholesterol, HDL-cholesterol, and non-HDL cholesterol.

Bruce Given, M.D., interim chief medical scientist at Arrowhead, added, “We continue to be encouraged by the full 48-week data from the SHASTA-2 study of plozasiran in patients with severe hypertriglyceridemia and as a result we are confidently advancing the program into multiple Phase 3 studies. We are pleased that over 90% of patients that received just two doses of plozasiran in the SHASTA-2 study achieved triglyceride levels below the level associated with increased risk of pancreatitis, and almost half of patients achieved triglyceride levels in the normal range, which is surprising given the high mean starting levels of almost 900 mg/dL. Two of Arrowhead’s planned Phase 3 studies are SHASTA-3 and SHASTA-4, which are both pivotal, year-long, placebo-controlled studies to evaluate the efficacy and safety of plozasiran in patients with severe hypertriglyceridemia, the same patient population as SHASTA-2. These studies are both on schedule to begin dosing over the coming months.”