Results from the phase 3 ESSENCE-TIMI 73b trial indicate that the medication olezarsen (marketed as Tryngolza) can normalize triglyceride (TG) levels in over 80% of patients suffering from hypertriglyceridemia after 12 months. The findings were presented at the European Society of Cardiology (ESC) Congress 2025 and suggest a significant advancement in treatment options for individuals with elevated triglyceride levels.
Olezarsen is an apolipoprotein C-III RNA-targeting therapy administered monthly. It received approval from the U.S. Food and Drug Administration (FDA) for treating familial chylomicronemia syndrome (FCS) in 2024. The trial demonstrated a statistically significant placebo-adjusted reduction of 61% and 58% in TG levels at the six-month mark for the 80 mg and 50 mg doses, respectively, in patients with moderate hypertriglyceridemia and elevated cardiovascular risk.
Dr. Brian Bergmark, principal investigator and interventional cardiologist at Brigham and Women’s Hospital, highlighted the importance of targeting triglyceride levels, stating, “High levels of triglycerides are an important risk factor for atherosclerotic cardiovascular disease and yet the effects of current therapies are modest. Olezarsen targets the mRNA of apolipoprotein C-III, which inhibits triglyceride clearance.”
The ESSENCE-TIMI 73b trial, initiated in 2022, was designed as a double-blind, randomized, placebo-controlled study. It assessed the safety and efficacy of olezarsen at doses of 50 mg and 80 mg among participants diagnosed with moderate hypertriglyceridemia, defined as TG levels ranging from 150 to 499 mg/dL, or severe hypertriglyceridemia, with levels of 500 mg/dL or greater. The trial enrolled a total of 1,478 patients from 160 sites across North America and Europe.
Participants were randomized in a 1:3 ratio to receive either olezarsen or a matching placebo every four weeks for 12 months. The primary outcome focused on the least-squares mean percent change in TG levels from baseline to six months, with a focus on patients experiencing moderate hypertriglyceridemia. Among the 1,349 participants analyzed, 254 received olezarsen at a 50 mg dose, 766 at 80 mg, and 329 received a placebo.
At the beginning of the study, the median age of participants was 64 years, with 40% being women and a median TG level of 238.5 mg/dL. The results indicated that the placebo-adjusted least-squares mean change in TG levels was −58.4 percentage points (95% confidence interval [CI], −65.1 to −51.7; P < .001) for the olezarsen 50 mg group and −60.6 percentage points (95% CI, −67.1 to −54.0; P < .001) for the 80 mg group. In comparison, the placebo group showed a mean change of only 2.8% (95% CI, −3.5 to 9.0). Furthermore, the trial reported that 85.0% of the olezarsen 50 mg group and 88.7% of the 80 mg group achieved TG levels below 150 mg/dL at six months, compared to only 12.5% in the placebo group (P < .001). Regarding safety, serious adverse events were noted in 9% of participants in the olezarsen 50 mg group, 14% in the 80 mg group, and 11% in the placebo group. The study also found that elevations in liver transaminase levels above the normal range occurred more frequently in the olezarsen groups, with rates of 34.2% for 50 mg and 38.3% for 80 mg, compared to 17.6% in the placebo group (both P < .001). However, clinically meaningful increases were rare across all treatment groups. Dr. Sam Tsimikas, senior vice president of global cardiovascular development at Ionis Pharmaceuticals, expressed optimism about the study’s results, stating, “The positive results of this study are an important step in bringing forward a potential new treatment for people with severely elevated triglycerides. Following the FDA approval and encouraging launch of olezarsen for people living with FCS, these data support olezarsen’s potential to benefit the much broader population of people living with severe hypertriglyceridemia.”
The findings of the ESSENCE-TIMI 73b trial mark a significant advancement in the treatment options available for patients struggling with hypertriglyceridemia, potentially offering a new lifeline for those at increased cardiovascular risk.