Lipid-efficacy RCT · N Engl J Med 2025
ESSENCE-TIMI 73b trial
Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia.
The bottom line
In patients with moderate hypertriglyceridemia and elevated cardiovascular risk, olezarsen significantly lowered triglyceride levels at 6 months compared with placebo, with similar rates of serious adverse events.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Olezarsen (N-acetylgalactosamine-conjugated antisense oligonucleotide targeting APOC3 mRNA), monthly subcutaneous, 50-mg or 80-mg dose cohorts
- Compared with
- Matching placebo
- People
- 1,349
- Who took part
- Patients with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter); median age 64 years, 40% women, median baseline triglyceride level 238.5 mg per deciliter (IQR 190.5 to 307.5)
- Design
- phase 3, international, double-blind, randomized, placebo-controlled trial
- Follow-up
- 6 months
- Main question
- Least-squares mean percent change in triglyceride level from baseline to 6 months among patients with moderate hypertriglyceridemia, reported as the placebo-adjusted change for each olezarsen dose group
Main result
At 6 months, the placebo-adjusted least-squares mean change in triglyceride level was -58.4 percentage points (95% CI, -65.1 to -51.7; P<0.001) in the olezarsen 50-mg group and -60.6 percentage points (95% CI, -67.1 to -54.0; P<0.001) in the olezarsen 80-mg group
Safety
The incidence of serious adverse events appeared to be similar across the trial groups.
In the trial's own words
“At 6 months, the placebo-adjusted least-squares mean change in triglyceride level was -58.4 percentage points (95% confidence interval [CI], -65.1 to -51.7; P<0.001) in the olezarsen 50-mg group and -60.6 percentage points (95% CI, -67.1 to -54.0; P<0.001) in the olezarsen 80-mg group.”
Quoted from the abstract of N Engl J Med 2025, checked word for word against PubMed. PubMed 40888739 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Olezarsen (Tryngolza) and volanesorsen
Common questions
What did the ESSENCE-TIMI 73b trial find?
In patients with moderate hypertriglyceridemia and elevated cardiovascular risk, olezarsen significantly lowered triglyceride levels at 6 months compared with placebo, with similar rates of serious adverse events.
Who was in ESSENCE-TIMI 73b?
1,349 people. Patients with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter); median age 64 years, 40% women, median baseline triglyceride level 238.5 mg per deciliter (IQR 190.5 to 307.5).
What was ESSENCE-TIMI 73b's main result?
At 6 months, the placebo-adjusted least-squares mean change in triglyceride level was -58.4 percentage points (95% CI, -65.1 to -51.7; P<0.001) in the olezarsen 50-mg group and -60.6 percentage points (95% CI, -67.1 to -54.0; P<0.001) in the olezarsen 80-mg group
Related trials
- CTX310 phase 1 (2025)A single dose of the CRISPR-Cas9 gene-editing therapy CTX310 was generally well tolerated and produced dose-dependent reductions in ANGPTL3 levels, supporting further clinical development for dyslipidemia.
- PALISADE (2025)In patients with persistent chylomicronemia, plozasiran (siRNA against APOC3) sharply lowered triglycerides and reduced acute pancreatitis episodes compared with placebo, with a similar overall adverse event rate but a signal for hyperglycemia in those with prediabetes/diabetes.
- PROLONG-ANG3 (2025)In adults with mixed dyslipidaemia on background statin therapy, solbinsiran 400 mg significantly reduced apoB levels compared with placebo and was generally well tolerated, though its effect on cardiovascular outcomes is still unknown.
- ARCHES-2 (2024)In adults with mixed hyperlipidemia, zodasiran (an RNAi therapy against ANGPTL3) produced significant, dose-dependent reductions in triglycerides and improvements in non-HDL-C, ApoB, and LDL-C compared with placebo, with a signal of transient HbA1c elevation in diabetic patients at the highest dose.
Get your LDL treated to a goal
Preval Health's protocols follow trials like this one. Licensed clinicians set your goal, prescribe and recheck until you reach it.
Get startedEducation only, not medical advice. Results describe the people in this trial and can differ for you. Talk with your clinician before starting or stopping any medicine. Back to all 106 trials.