Madrid, Spain – 30 August 2025: Olezarsen decreased levels of triglycerides compared with placebo in patients with moderate hypertriglyceridaemia and elevated cardiovascular risk, according to a late-breaking trial presented in a Hot Line session today at ESC Congress 2025 and simultaneously published in New England Journal of Medicine.1
“High levels of triglycerides are an important risk factor for atherosclerotic cardiovascular disease (ASCVD) and yet the effects of current therapies are modest,” explained Principal Investigator, Doctor Brian Bergmark from the TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. He continued: “Olezarsen targets the mRNA of apolipoprotein C-III, which inhibits triglyceride clearance. Olezarsen has been shown to lower triglyceride levels in small phase II trials and in patients with very high triglyceride levels.2−4 We investigated the efficacy and safety of olezarsen in patients with moderate hypertriglyceridaemia at high ASCVD risk in the ESSENCE-TIMI 73b trial.”
The placebo-controlled, double-blind phase III ESSENCE-TIMI 73b trial was conducted at 160 sites in North America and Europe. The trial included adult patients with moderate hypertriglyceridaemia (triglycerides 150−499 mg/dL) and elevated cardiovascular risk due to an established diagnosis of ASCVD or increased ASCVD risk as a result of type 2 diabetes mellitus and age ≥55 years. Patients were expected to be on optimised stable low-density lipoprotein-cholesterol (LDL-C)-lowering therapy at enrolment. The ESSENCE-TIMI 73b trial also included patients with severe hypertriglyceridaemia (triglycerides ≥500 mg/dL). The primary analytic cohort was patients with moderate hypertriglyceridaemia as patients with severe hypertriglyceridaemia are being studied in dedicated, separate trials.
The primary analysis population included 1,349 patients with moderate hypertriglyceridaemia and elevated cardiovascular risk who were randomised to olezarsen 50 mg (n=254), olezarsen 80 mg (n=766) or placebo (n=329) given every 4 weeks via subcutaneous injection for 12 months. The primary endpoint was the percent change from baseline in triglyceride levels at 6 months compared with placebo.
The primary analysis population had a median age of 64 years and 40% were women. The median triglyceride level at baseline was 238.5 mg/dL.
At 6 months, olezarsen significantly reduced levels of triglycerides: the placebo-adjusted least-squares mean difference in percent change from baseline was −58.4 percentage points for olezarsen 50 mg and −60.6 percentage points for olezarsen 80 mg (both p<0.001 vs. placebo).
In the placebo group, 12.5% of patients had triglyceride levels <150 mg/dL at 6 months, compared with 85.0% of patients on olezarsen 50 mg and 88.7% on olezarsen 80 mg (p<0.001 for both). At 12 months, the proportions were 20.6%, 82.8% and 85.0% for placebo, olezarsen 50 mg and olezarsen 80 mg, respectively (p<0.001 for both vs. placebo). Olezarsen significantly reduced levels of other lipoproteins − remnant cholesterol, non-high-density lipoprotein cholesterol and apolipoprotein B – with no significant effect on LDL-C.
The incidence of serious adverse events appeared similar: 9% with olezarsen 50 mg, 14% with olezarsen 80 mg and 11% with placebo. Liver transaminase elevations to any degree above the upper limit of the normal range were more common with olezarsen 50 mg (34.2%) and olezarsen 80 mg (38.3%) than with placebo (17.6%) (both p<0.001); however, clinically meaningful increases were rare and similar across groups.
Summarising, Doctor Bergmark said: “In a population with moderate hypertriglyceridaemia and elevated cardiovascular risk, monthly olezarsen resulted in substantial triglyceride lowering greater than would be expected from currently available therapies, with more than 80% of patients treated with olezarsen achieving normal triglyceride levels.”
ENDS
Notes to editor
This press release accompanies both a presentation and an ESC press conference at ESC Congress 2025.
It does not necessarily reflect the opinion of the European Society of Cardiology.
Funding: The trial was sponsored by Ionis Pharmaceuticals.
Disclosures: Doctor Bergmark reports grant support through his institution from Ionis, Pfizer, Abbott Vascular, Philips, Inari, AstraZeneca, MedImmune and Amgen; and consulting/personal fees from Shockwave, Abbott Vascular, Abiomed, Bain Life Sciences, Bolt, Terumo, SpectraWAVE, CSI and Endovascular Engineering.
References and notes:
1‘Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: the Essence-TIMI 73b trial’ presented during HOT LINE 4 on 30 August 2025 at 16:45 to 16:55 in Madrid (Main Auditorium) and simultaneously published in New England Journal of Medicine
2Bergmark BA, Marston NA, Prohaska TA, et al. Olezarsen for hypertriglyceridemia in patients at high cardiovascular risk. N Engl J Med. 2024;390:1770−1780.
3Tardif JC, Karwatowska-Prokopczuk E, Amour ES, et al. Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur Heart J. 2022;43:1401−1412.
4Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E, et al. Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome. N Engl J Med. 2024;390:1781−1792.
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