Redemplo cuts triglycerides, pancreatitis risk in severe hypertriglyceridemia

Redemplo (plozasiran) resulted in a reduction of triglycerides and also reduced the rate of acute pancreatitis in patients with severe hypertriglyceridemia (sHTG) in top-line data from two phase 3 trials.

Severe hypertriglyceridemia (sHTG) is a condition that increases the risk of acute pancreatitis (AP). It is characterized by triglyceride levels greater than 500 milligrams per deciliter (mg/dL); normal triglyceride levels are less than 150 mg/dL in healthy adults. Elevated triglycerides can also increase the risk of atherosclerotic cardiovascular disease.

Developed by Arrowhead Pharmaceuticals, Redemplo already available to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS), a rare disease that causes extremely high triglycerides. It is administered with a 25 mg subcutaneous injection every three months.

Redemplo was approved in November 2025, and it launched with an annual wholesale acquisition cost of $60,000. The company offers a $0 copay program for patients with commercial insurance. A care coordinator can help patients navigate insurance coverage for Redemplo

Redemplo is a small interfering RNA (siRNA) medicine designed to suppress the production of APOC3, a protein produced in the liver that raises triglyceride levels by slowing their breakdown and clearance. Redemplo uses the company’s proprietary Targeted RNAi Molecule (TRiM) platform, which is able to harness RNAi to silence specific messenger RNAs and reduce the production of proteins that cause disease.

Between SHASTA-3 and SHASTA-4, approximately 750 participants were randomized to receive four doses (once every 3 months) of 25 mg Redemplo or placebo. The primary endpoint was percent change in fasting serum triglyceride levels from baseline to month 12 compared with placebo. After month 12, eligible participants are offered an opportunity to continue in an optional open-label extension.

In the phase 3 trials, Redemplo led to median triglyceride reductions of 79% (the SHASTA-3 trial) and 81% (the SHASTA-4) at month 12 compared with placebo. Patients in the placebo arm saw a median reduction of triglycerides of approximately 27%. In a pre-planned pooled analysis of acute pancreatitis events in both trials, there was a statistically significant reduction in both the rate of pancreatitis and the total incidence rate in patients treated with Redemplo.

In the broad study population of severe hypertriglyceridemia with or without a prior history of acute pancreatis, cumulative events were reduced by 78% in treated patients. In a subset of patients with triglycerides above 880 mg/dL and a prior medical history of acute pancreatitis, plozasiran treatment demonstrated a 100% reduction in Redemplo events compared with placebo.

In both trials, the overall treatment-emergent adverse events were similar to prior studies. There were no clinically meaningful differences in routine clinical laboratory measurements and no new safety signals. There were no statistically significant differences between Redemplo and placebo in mean liver fat content assessed by MRI-PDFF in a prespecified subgroup and no clinically meaningful adverse changes in liver enzymes. There were no cases of hypersensitivity and no signal for low platelet count.

“Plozasiran continues to demonstrate deep and durable pharmacodynamic effects with a consistently favorable safety and tolerability profile, including a highly encouraging liver safety profile,” James Hamilton, M.D., chief medical officer and head of R&D at Arrowhead, said in a news release.

Results from the SHASTA-3 and SHASTA-4 studies will be presented at the upcoming European Society of Cardiology Congress in August 2026 with publication in the second half of this year.

Company officials said in a news release they plan to file an sNDA in the United States before the end of this year.

Redemplo is also being studied in patients with mixed hyperlipidemia