Arrowhead Reports 78% Reduction in Pancreatitis Episodes With Plozasiran
Key Facts
On November 7, 2026, Arrowhead Pharmaceuticals presented results from a pooled analysis of the SHASTA-3 and SHASTA-4 studies, showing that plozasiran reduced the rate of adjudicated acute pancreatitis episodes by 78% versus placebo in patients with severe hypertriglyceridemia. The company presented the results during the American Heart Association’s scientific sessions in Chicago. The finding is significant because it shifts the focus from lowering triglycerides to a clinical outcome associated with the disease. The studies included 757 adults who were randomly assigned to the drug or placebo. Participants received plozasiran at a dose of 25 mg every three months.
The reduction was larger among patients who had experienced pancreatitis in the five years before screening, reaching 91% versus placebo. In the group with a history of the disease and baseline triglyceride levels between 500 and 880 mg/dL, the episode rate fell by 82%. Among those with a prior history and triglyceride levels of at least 880 mg/dL, the group receiving plozasiran recorded no episodes among 35 patients. In the corresponding placebo group, five episodes occurred among 17 patients. These results highlight variation in response according to participants’ triglyceride levels and medical history.
The episode findings add to previously published results on triglyceride reductions from the two studies. At month 12, the median reduction from baseline was 79% in SHASTA-3 and 81% in SHASTA-4. The proportion of patients whose triglyceride levels fell below 500 mg/dL reached 91% and 93%, respectively, with plozasiran. In the two placebo groups, the proportions were 51% and 50%, respectively. Chief Executive Christopher Anzalone said what may matter most to patients and physicians is the “substantial reduction in acute pancreatitis.”
Pooled safety data showed that treatment-emergent adverse events were reported in 73% of patients in each of the plozasiran and placebo groups. Serious adverse events occurred in 8.3% of patients receiving the drug, compared with 10% of those receiving placebo. Worsening glycemic control was reported in 14% of the drug group and 8.7% of the comparator group. In open-label follow-up data for patients with familial chylomicronemia syndrome, median reductions from baseline in triglycerides and APOC3 remained at 76% and 89%, respectively, with total treatment extending to 36 months. These figures provide context for the clinical results over a longer treatment period, but relate to the PALISADE program and a different patient population.
The company also presented early interim results for ARO-DIMER-PA, an investigational program for patients with mixed dyslipidemia. Phase 1/2a results followed a single dose and showed mean reductions from baseline in low-density lipoprotein cholesterol ranging from 26% to 65%, and median reductions in triglycerides ranging from 56% to 78% across the available dose groups and follow-up periods. These changes are calculated from baseline and are not adjusted against placebo. The presentation covered five single doses: 25, 50, 100, 200 and 400 mg, with 21 participants receiving treatment and 10 receiving placebo. No deaths or serious events were reported, but one participant in the 400 mg group experienced Grade 3 syncope six hours after the dose.
Arrowhead plans to submit a supplemental new drug application to the U.S. Food and Drug Administration before the end of 2026, seeking to expand plozasiran’s use to a broader population of people with severe hypertriglyceridemia, with the benefit of a priority review voucher. The drug is currently marketed as REDEMPLO, and the agency approved it on November 18, 2025, to lower triglycerides in adults with familial chylomicronemia syndrome alongside a low-fat diet. The anticipated step targets the broader severe hypertriglyceridemia population. Arrowhead shares closed at $58.16 on November 6, the session before the results announcement. The closing-price data provided do not include a price for any session after the announcement.