Arrowhead(ARWR) RNA Therapeutic 'Plicarean'… Up to 83% reduction in triglycerides · 0 cases of pancreatitis

American biotech company Arrowhead Pharmaceuticals (ARWR) is developing the RNA interference therapy drug “plozasiran,” whose long-term efficacy and safety in treating severe hypertriglyceridemia have been confirmed again. In a two-year extension clinical trial, the drug showed triglyceride reductions of more than 80% and suppressed the occurrence of acute pancreatitis. With these results announced, the drug is emerging as a new treatment option in the cardiovascular metabolic disease market.

On the 29th (local time), Arrowhead released the results of its Phase 2 open-label extension study of plozasiran. The data were presented at the American College of Cardiology’s annual scientific meeting and published in the Journal of the American College of Preventive Cardiology. Christie Ballantyne, MD, from Baylor College of Medicine, who led the study, said: “The ‘triglyceride-lowering effect’ and ‘safety’ confirmed in the long-term data are very encouraging,” adding, “Especially in a high-risk patient population, there were no cases of acute pancreatitis within two years—this is an important signal.”

In this study, the median triglyceride level decreased by 83% among patients with severe hypertriglyceridemia, and 96% of patients reached below the acute pancreatitis risk baseline of 500 mg/dL. A 67% reduction effect was also confirmed in the general hypertriglyceridemia patient group. In addition, a consistent improvement was seen in atherosclerosis-related lipid markers closely associated with cardiovascular disease, including residual cholesterol, non-HDL cholesterol, and apolipoprotein B.

Plozasiran works based on RNA interference technology by suppressing the production of apolipoprotein C-III in the liver. APOC3 is a key protein that obstructs triglyceride breakdown; blocking its action promotes the clearance of triglycerides in the body. In fact, it is known that people with hereditary APOC3 loss of function have lower triglyceride levels and a reduced risk of cardiovascular disease.

In terms of safety, results consistent with previous studies were also obtained. Glycemic indicators, including glycated hemoglobin, remained stable, and no clinically meaningful adverse reactions were found. Although some reports included diabetes, COVID-19, upper respiratory tract infections, and low back pain, their levels were similar to those in prior trials. Liver fat content also showed no significant change.

Arrowhead CEO Christopher Anzalone said: “After plozasiran has already received FDA approval for the treatment of familial chylomicronemia, it is now bringing meaningful change for real patients,” and “In the future, it has the potential to expand the indication to the entire severe hypertriglyceridemia field.” He further emphasized: “With our TRiM platform RNAi therapy, it can not only be used for cardiovascular metabolic diseases, but also expanded to multiple types of difficult-to-treat diseases.”

The company is currently conducting global Phase 3 clinical trials (SHASTA-3, SHASTA-4, MUIR-3), targeting completion in mid-2026. After that, it plans to submit additional drug marketing approval applications to the U.S. Food and Drug Administration by the end of the same year.

Hypertriglyceridemia refers to a disease in which triglyceride levels in the blood rise to 500 mg/dL or higher; in severe cases, it increases the risk of recurrent acute pancreatitis and cardiovascular disease. In particular, familial chylomicronemia, in which triglyceride levels can spike to more than 880 mg/dL, is a rare disease with limited existing treatment options. The industry is watching the potential for plozasiran to become a “game changer” that addresses these unmet needs.

Commentary: Plozasiran goes beyond a simple lipid-lowering drug; as an RNA-based precision therapy, it has demonstrated scalability, so it is regarded as a candidate drug that could potentially change the paradigm of cardiovascular treatment in the future.