Research presented at the European Society of Cardiology (ESC) Congress 2025 indicated that *olezarsen*, marketed as *Tryngolza*, effectively normalizes triglyceride (TG) levels in over 80% of patients suffering from hypertriglyceridemia (HTG). This promising outcome stems from the phase 3 *ESSENCE-TIMI 73b* trial, which showcased the treatment’s potential to significantly reduce TG levels among individuals at elevated cardiovascular risk.
The trial involved 1,478 participants across North America and Europe, who were randomized into either a 50 mg or 80 mg monthly olezarsen treatment group, or a placebo group. Results demonstrated a statistically significant placebo-adjusted reduction in TG levels of 61% for the 80 mg dose and 58% for the 50 mg dose after 6 months. Participants with moderate HTG, defined by TG levels between 150 and 499 mg/dL, achieved a median baseline TG level of 238.5 mg/dL.
Brian Bergmark, MD, principal investigator and Interventional Cardiologist at Brigham and Women’s Hospital, emphasized the significance of these findings. He noted, “High levels of triglycerides are an important risk factor for atherosclerotic cardiovascular disease, and yet the effects of current therapies are modest.” The therapy targets the mRNA of apolipoprotein C-III, a key protein that inhibits the clearance of triglycerides.
Trial Design and Key Findings
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 HTG. The primary outcome focused on the least-squares mean percent change in TG levels from baseline to 6 months.
In the analysis, 1,349 participants were included in the primary evaluation. Among these, 254 received the 50 mg dose, 766 were administered the 80 mg dose, and 329 received a placebo. The findings revealed that 85% of the olezarsen 50 mg group and 88.7% of the 80 mg group achieved TG levels below 150 mg/dL at the 6-month mark, compared to just 12.5% in the placebo group.
The results showed a placebo-adjusted least-squares mean change in TG levels of -58.4 percentage points for olezarsen 50 mg and -60.6 percentage points for olezarsen 80 mg, both statistically significant (P < .001). The overall least-squares mean change from baseline was noted as -55.6% for the 50 mg group, -57.8% for the 80 mg group, and only 2.8% for the placebo group.
Safety and Implications for Treatment
Safety data indicated that serious adverse events were reported in 9% of participants receiving the 50 mg dose, 14% in the 80 mg group, and 11% in the placebo cohort. Liver transaminase elevations were more prevalent in the treatment groups compared to placebo, with 34.2% for the 50 mg group and 38.3% for the 80 mg group, versus 17.6% for placebo. Despite these findings, the risk of clinically meaningful increases was considered rare and similar across all groups.
The results of this trial are particularly noteworthy following the US Food and Drug Administration (FDA) approval of olezarsen for familial chylomicronemia syndrome (FCS) in 2024. Sam Tsimikas, MD, Senior Vice President of Global Cardiovascular Development at Ionis Pharmaceuticals, stated, “The positive results of this study are an important step in bringing forward a potential new treatment for people with severely elevated triglycerides.”
With the growing body of evidence supporting olezarsen’s efficacy, this treatment may offer significant benefits to a broader population suffering from severe hypertriglyceridemia (sHTG). As the medical community continues to explore innovative therapies, olezarsen stands out as a potential game-changer in managing high triglyceride levels and reducing cardiovascular risk.
