August 30, 2025
2 min read
Key takeaways:
- A monthly injection of olezarsen reduced triglyceride levels in adults with elevated cardiovascular risk.
- More than 80% of patients assigned olezarsen achieved a normal triglyceride level at 6 months.
Monthly olezarsen reduced triglyceride levels by up to 60% at 6 months among patients with moderate hypertriglyceridemia and elevated cardiovascular risk.
Treatment with olezarsen (Tryngolza, Ionis Pharmaceuticals) also lowered levels of remnant cholesterol, non-HDL cholesterol and apolipoprotein B, with no change in LDL cholesterol, according to results from the phase 3 Essence-TIMI 73b trial.
A monthly injection of olezarsen reduced triglyceride levels in adults with elevated cardiovascular risk. Image: Adobe Stock
“This triglyceride effect was greater than is possible with current standard of care therapies,” Brian A. Bergmark, MD, with the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital and Harvard Medical School, said during a press conference at the European Society of Cardiology Congress. “These findings support the efficacy and safety of olezarsen for triglyceride lowering in a broad population of patients with moderately elevated triglycerides.”
Efficacy, safety in a broader population
Brian A. Bergmark
Elevated levels of triglycerides are a risk factor for atherosclerotic CVD, but highly effective therapies are “still lacking,” Bergmark said during the press conference.
Olezarsen is an antisense oligonucleotide that targets the messenger RNA for apolipoprotein C-III, which is a target for triglyceride lowering.
Olezarsen was approved by the FDA in 2024 for the treatment of familial chylomicronemia syndrome.
“Olezarsen is approved in the U.S. for triglyceride lowering in adults with familial chylomicronemia syndrome. However, its efficacy and safety in a broader population of patients with hypertriglyceridemia and elevated cardiovascular risk are not yet established. That’s what led us to this trial,” Bergmark said.
The phase 3, double-blind, randomized, placebo-controlled trial included patients with moderate hypertriglyceridemia (150-499 mg/dL) and elevated CV risk, due to established ASCVD or type 2 diabetes plus age of at least 55 years, or severe hypertriglyceridemia ( 500 mg/dL). The median age of patients was 64 years, 40% were women and the median baseline triglyceride level was 238.5 mg/dL.
Bergmark reported results from 1,349 patients who were randomly assigned to olezarsen 50 mg, olezarsen 80 mg or placebo, administered every 4 weeks via subcutaneous injection for 12 months.
The data were presented during a Hot Line session and simultaneously published in The New England Journal of Medicine.
Change in triglyceride levels
The primary outcome was placebo-adjusted least-squares mean change in triglyceride level from baseline to 6 months. Compared with placebo, the mean change at 6 months was –58.4 percentage points among patients assigned olezarsen 50 mg (P < .001) and –60.6 percentage points among those assigned 80 mg (P < .001), according to the results.
Among those with moderate hypertriglyceridemia, 12.5% in the placebo achieved a normal triglyceride level at 6 months, defined as less than 150 mg/dL, compared with 85% in the olezarsen 50 mg group and 88.7% in the 80 mg group (P < .001 for both vs. placebo), Bergmark said.
Reductions with olezarsen treatment were up to 22% for non-HDL cholesterol, 57% for VLDL cholesterol, 68% for remnant cholesterol and 15% for ApoB, and there was no change in LDL cholesterol with either dose compared with placebo, Bergmark said during the press conference.
There were no major safety concerns with olezarsen treatment, Bergmark said. The researchers reported similar rates of adverse events (72.8%-76.7% with olezarsen vs. 72.1% with placebo) and serious adverse events (9.4%-13.6% vs. 11.4%) between the treatment groups. There were more injection-site reactions with olezarsen and increases in liver aminotransferase levels were rare and consistent across the treatment groups, according to the results.
“Determining whether these changes to the lipid profile would translate into a clinical benefit with respect to cardiovascular outcomes would require a dedicated trial,” the researchers wrote in NEJM.
Reference:
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Sources/Disclosures
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Source:
Bergmark B, et al. Hot line 4. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2025; Madrid (hybrid meeting).
Disclosures:
The Essence-TIMI 73b trial was funded by Ionis Pharmaceuticals. Bergmark reports receiving grant support through his institution from Abbott Vascular, Amgen, AstraZeneca, Inari, Ionis, MedImmune, Pfizer and Philips and consultant/personal fees from Abbott Vascular, Abiomed, Bain Life Sciences, Bolt, CSI, Endovascular Engineering, Shockwave, SpectraWAVE and Terumo.
