FDA APPROVES RNA-TARGETED ANTISENSE OLIGONUCLEOTIDE TO TREAT HIGH TRIGLYCERIDES
Tryngolza (olezarsen) lowers triglycerides by inhibiting apoC-III
Straight Healthcare
August 2026
August 2026
Severe hypertriglyceridemia (sHTG), typically defined as fasting triglycerides (TG) of 500 mg/dL or higher, raises the risk of acute pancreatitis and is usually managed with lifestyle measures plus older lipid-lowering drugs. Approved pharmacologic options have long included fibrates (e.g., fenofibrate, gemfibrozil), prescription omega-3 fatty acids (e.g., icosapent ethyl, omega-3-acid ethyl esters), and niacin. These agents reduce TG to varying degrees but often leave patients with genetic or refractory severe hypertriglyceridemia, including familial chylomicronemia syndrome (FCS), without adequate control. The FDA recently expanded Tryngolza (olezarsen) indications to include adults with sHTG, as an adjunct to diet to reduce the risk of acute pancreatitis. Tryngolza is an antisense oligonucleotide conjugated to N-acetylgalactosamine, which allows it to be taken up by hepatocytes, where it binds apolipoprotein C-III (apoC-III) messenger RNA and promotes its degradation. Lowering ApoC-III levels increases the clearance of triglyceride-rich lipoproteins.
Tryngolza's efficacy in sHTG was evaluated in two randomized, double-blind, placebo-controlled trials (Trials 2 and 3; N=1,061) where adults with fasting TG of at least 500 mg/dL (pooled mean baseline fasting TG was 1,116 mg/dL) on optimized, stable background lipid-lowering therapy were randomized to monthly subcutaneous Tryngolza 50 mg, 80 mg, or placebo. At Month 6, placebo-corrected reductions in fasting TG were 63% (50 mg) and 72% (80 mg) in Trial 2 and 49% and 55% in Trial 3 (p<0.0001 for all comparisons). An integrated analysis also found lower adjudicated rates of acute pancreatitis events with Tryngolza versus placebo. Dosing for sHTG is 50 mg subcutaneously once monthly, with an increase to 80 mg if additional TG lowering is needed. The most common adverse reaction was injection site reactions. Tryngolza can also lower platelet counts (mean declines of about 6% to 10% through Week 53) and raise liver enzymes, more often at 80 mg (enzyme elevations of at least 3 times the upper limit of normal in 7% versus 3% with 50 mg or placebo). Liver testing before initiation or dose increase is advised, and serious hepatic injury warrants discontinuation.
Tryngolza is indicated as an adjunct to diet to reduce TG in adults with FCS and to reduce TG and the risk of acute pancreatitis in adults with sHTG. As with other specialty lipid therapies, cost will limit routine use. In practice, it will mainly be reserved for patients who remain at high TG-related risk despite diet and less expensive options such as fibrates and prescription omega-3s.
Tryngolza's efficacy in sHTG was evaluated in two randomized, double-blind, placebo-controlled trials (Trials 2 and 3; N=1,061) where adults with fasting TG of at least 500 mg/dL (pooled mean baseline fasting TG was 1,116 mg/dL) on optimized, stable background lipid-lowering therapy were randomized to monthly subcutaneous Tryngolza 50 mg, 80 mg, or placebo. At Month 6, placebo-corrected reductions in fasting TG were 63% (50 mg) and 72% (80 mg) in Trial 2 and 49% and 55% in Trial 3 (p<0.0001 for all comparisons). An integrated analysis also found lower adjudicated rates of acute pancreatitis events with Tryngolza versus placebo. Dosing for sHTG is 50 mg subcutaneously once monthly, with an increase to 80 mg if additional TG lowering is needed. The most common adverse reaction was injection site reactions. Tryngolza can also lower platelet counts (mean declines of about 6% to 10% through Week 53) and raise liver enzymes, more often at 80 mg (enzyme elevations of at least 3 times the upper limit of normal in 7% versus 3% with 50 mg or placebo). Liver testing before initiation or dose increase is advised, and serious hepatic injury warrants discontinuation.
Tryngolza is indicated as an adjunct to diet to reduce TG in adults with FCS and to reduce TG and the risk of acute pancreatitis in adults with sHTG. As with other specialty lipid therapies, cost will limit routine use. In practice, it will mainly be reserved for patients who remain at high TG-related risk despite diet and less expensive options such as fibrates and prescription omega-3s.
