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Triglyceride Management and Pancreatitis Risk, With Christie M. Ballantyne, MD
Christie M. Ballantyne, MD, discusses the role of plozasiran in managing elevated triglycerides and reducing pancreatitis risk.
Triglyceride Management and Pancreatitis Risk, With Christie M. Ballantyne, MD
New results from two Phase 2 trials—SHASTA-2 and MUIR—show that plozasiran, an investigational siRNA therapy targeting hepatic APOC3, delivers a substantial reduction in triglyceride-rich lipoprotein particles (TRL-P) and drives a favorable shift in lipoprotein composition and size in patients with hypertriglyceridemia.1
Presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, patients with severe hypertriglyceridemia (HTG) or mixed dyslipidemia received plozasiran 10, 25, or 50 mg subcutaneously at baseline and again at week 12. At the 25 mg dose, plozasiran significantly reduced TRL-P by ~50% in both trials.
“When you see high triglycerides, sometimes the low-density lipoprotein cholesterol (LDL-C) goes up. With nuclear magnetic resonance (NMR) data, you’re changing the particle, so you have an increase in the large particles and a reduction in small, dense LDL particles,” Christie M. Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine, told HCPLive. “Reduction in small, dense LDL particles may be particularly atherogenic, but these triglyceride particles per particle might be worse for the common person. They have more LDL particles, but people with high triglycerides have different types of particles.”
Importantly, while total LDL-P remained stable, there was a shift toward larger LDL particles, considered less atherogenic. Small LDL-P declined by 20–22%, while large LDL-P increased up to 103% in MUIR. HDL particle concentration also improved, driven by increases in large HDL-P.
Insulin resistance also improved in both studies, by 24% in SHASTA-2 and 9% in MUIR, further supporting the cardiometabolic potential of plozasiran. Ballantyne noted that high triglyceride levels, particularly over 1000 mg/dL, pose an acute pancreatitis risk and could signal conditions like familial chylomicronemia syndrome (FCS).
In a recent analysis of 1.2 million patients, Ballantyne found more than 90% experienced triglyceride reductions with standard treatment, but about 1 in 5,500 had persistent chylomicronemia. Among those individuals, 26% developed pancreatitis, underscoring the need for close monitoring and targeted therapy.
“The other alarm feature is, if they've had a history of pancreatitis, you better worry about that patient, because it's like secondary prevention,” Ballantyne told HCPLive. “To keep it simpler, when you see the 1000 mg/dL, you know you need to have some alarms going off in terms of needing special attention.”
Relevant disclosures for Ballantyne include Arrowhead, AstraZeneca, Eli Lilly and Company, Abbott Diagnostics, NewAmsterdam, and others.
