Results from the phase 3 ESSENCE-TIMI 73b trial indicate that treatment with olezarsen (marketed as Tryngolza) effectively normalizes triglyceride (TG) levels in over 80% of patients suffering from hypertriglyceridemia (HTG) after 12 months of administration. This promising data was presented at the European Society of Cardiology (ESC) Congress 2025, showcasing the potential of olezarsen, an RNA-targeting therapy that inhibits apolipoprotein C-III, to significantly impact patient outcomes.
The trial results revealed that olezarsen, which gained FDA approval in 2024 for familial chylomicronemia syndrome (FCS), led to a statistically significant reduction in TG levels. At the 6-month mark, patients receiving the 80 mg and 50 mg doses showed a placebo-adjusted decrease of 61% and 58%, respectively. According to principal investigator Brian Bergmark, MD, these findings highlight a significant advancement in treatment for patients at elevated cardiovascular risk.
Trial Design and Participant Demographics
The ESSENCE-TIMI 73b trial was a double-blind, randomized, placebo-controlled study designed to evaluate the safety and efficacy of olezarsen in patients with moderate to severe hypertriglyceridemia. Hypertriglyceridemia was defined as TG levels between 150 and 499 mg/dL, while severe hypertriglyceridemia was classified as levels exceeding 500 mg/dL. The trial enrolled participants across 160 sites in North America and Europe, with 1,478 individuals randomized in a 1:3 ratio to receive either olezarsen or a matching placebo.
Out of the total participants, 1,349 were included in the primary analysis, with 254 receiving the 50 mg dose, 766 receiving the 80 mg dose, and 329 receiving placebo. The median age of participants was 64 years, with 40% being women and a median baseline TG level of 238.5 mg/dL.
The primary outcome of interest was the least-squares mean percent change in TG levels from baseline to 6 months. The findings indicated that the olezarsen 50 mg group experienced a placebo-adjusted change of −58.4% (95% confidence interval [CI], −65.1 to −51.7; P < .001) while the 80 mg group saw a change of −60.6% (95% CI, −67.1 to −54.0; P < .001).
Safety and Efficacy Observations
The results of the trial indicated that a noteworthy 85.0% of participants in the olezarsen 50 mg group and 88.7% in the olezarsen 80 mg group achieved TG levels below 150 mg/dL at 6 months, compared to only 12.5% in the placebo group (P < .001). In terms of safety, serious adverse events occurred in 9% of the participants receiving the 50 mg dose, 14% for the 80 mg dose, and 11% in the placebo group. Additionally, elevations in liver transaminase levels were observed more frequently in those receiving olezarsen (34.2% for 50 mg and 38.3% for 80 mg) compared to the placebo group (17.6%) (both P < .001). Nevertheless, clinically meaningful increases in liver enzymes were rare across all groups. Dr. Sam Tsimikas, senior vice president for global cardiovascular development at Ionis Pharmaceuticals, emphasized the study’s results as a significant step towards providing a new treatment option for individuals with markedly elevated triglycerides. He noted that following the FDA approval of olezarsen for patients with FCS, the trial data supports its potential benefits for a broader population suffering from severely elevated triglycerides (sHTG).
The complete findings from the ESSENCE-TIMI 73b trial will be crucial in shaping future treatment protocols for hypertriglyceridemia. As more data becomes available, healthcare providers may have the opportunity to offer improved management strategies for patients at risk of cardiovascular diseases linked to high triglyceride levels.
