Hot Line 4: ESSENCE-TIMI 73b
31 Aug 2025
Hot Line ESC Congress 2025 Olezarsen in patients with hypertriglyceridaemia at high CV risk: ESSENCE-TIMI 73b
Doctor Brian Bergmark (Brigham and Women's Hospital, Harvard Medical School - Boston, USA) presented results from the ESSENCE-TIMI 73b trial investigating the antisense oligonucleotide targeting APOC3 mRNA, olezarsen, in patients with moderate hypertriglyceridaemia at high atherosclerotic cardiovascular disease (ASCVD) risk.
The analysis included 1,349 patients with triglycerides 150–499 mg/dl and elevated cardiovascular risk (ASCVD or type 2 diabetes plus age ≥55 years) on optimised low-density lipoprotein-cholesterol (LDL-C)-lowering therapy. The median age was 64 years, 40% were women and the median triglyceride level was 238.5 mg/dl.
At 6 months, the placebo-adjusted least-squares mean difference in percent change in triglycerides 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.
Summarising, Dr. 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.”
