Key result
Olezarsen and plozasiran lower triglycerides via apoC-III reduction but warrant liver and glycemic monitoring.
Why the study?
Olezarsen and plozasiran have recently been approved for familial chylomicronemia syndrome and evaluated in trials across hypertriglyceridemia, warranting a review of their lipid-lowering effects and safety.
Do olezarsen and plozasiran safely reduce triglyceride levels and improve lipid parameters in patients with hypertriglyceridemia?
Do olezarsen and plozasiran safely reduce triglyceride levels and improve lipid parameters in patients with hypertriglyceridemia?
Olezarsen and plozasiran are novel, effective, and generally well-tolerated therapies for lowering triglycerides in patients with hypertriglyceridemia, though their impact on hard clinical outcomes like ASCVD and pancreatitis remains to be established.
Supports triglyceride reduction in hypertriglyceridemia; extends apoC-III data but leaves cardiovascular outcomes open.
Hypertriglyceridemia is a prevalent lipid disorder associated with residual atherosclerotic cardiovascular disease (ASCVD) risk and increased risk of acute pancreatitis at triglyceride (TG) levels above 1000 mg/dL. Causes of hypertriglyceridemia are multifactorial and may be a result of secondary causes (Western diet, alcohol, medications, uncontrolled diseases/disorders), genetic disorders, or a combination of both. Two novel medications (olezarsen, plozasiran), which inhibit hepatic production of apoC-III mRNA and increase TG clearance, have recently been approved to reduce TG levels in adults with familial chylomicronemia syndrome (FCS). Both olezarsen and plozasiran have been evaluated in randomized, placebo-controlled, clinical trials in patients with varying degrees of hypertriglyceridemia. In this review, we report the lipid-lowering effects and safety of both olezarsen and plozasiran from clinical trials in patients with hypertriglyceridemia. Based on available data, both agents are associated with significant TG-lowering effects via reductions in apoC-III, as well as favorable effects on other lipid parameters. Overall, both agents appear generally well tolerated, although monitoring of liver enzymes and glycemic control is warranted for both agents, and additional monitoring of platelet counts for olezarsen. Future clinical trials are needed to assess whether the TG-lowering effects of each agent are associated with reduced risk of pancreatitis and ASCVD events.
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Kelly et al. (2026) conducted a review in Hypertriglyceridemia. Olezarsen and Plozasiran was evaluated on Lipid-lowering effects and safety. Olezarsen and plozasiran significantly lower triglyceride levels via apoC-III reduction and are generally well tolerated, though monitoring of liver enzymes and glycemic control is warranted.
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