Trial results for Olezarsen in adults with hypertriglyceridemia and atherosclerotic cardiovascular disease were posted on ClinicalTrials.gov on 2026-04-23. The Phase 2 study showed that Olezarsen 80 mg reduced fasting triglyceride levels by -60.92% at Month 6, compared to a -7.77% reduction in the placebo group.
Background
The study aimed to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo at Months 6 and 12, and the proportion of participants who achieved different thresholds in fasting TG. Other objectives included evaluating effects on apolipoprotein C-III (apoC-III), very low-density lipoprotein cholesterol (VLDL-C), and remnant cholesterol.
Trial design
The Phase 2 study (NCT05355402) was a randomized, placebo-controlled trial that enrolled 154 adult participants. The study investigated olezarsen in individuals with hypertriglyceridemia, atherosclerotic cardiovascular disease, and/or severe hypertriglyceridemia. Participants were assigned to receive either olezarsen 50 mg, olezarsen 80 mg, or placebo. The primary objectives focused on the percent change in fasting triglyceride levels at Months 6 and 12 compared to placebo, and the proportion of participants achieving specific fasting triglyceride thresholds.
Key results
The trial demonstrated significant reductions in fasting triglyceride levels with olezarsen compared to placebo.
- At Month 6, the least squares mean percent change from baseline in fasting TG was -7.77% for placebo, -57.05% for Olezarsen 50 mg, and -60.92% for Olezarsen 80 mg. The least squares mean difference for Olezarsen 50 mg vs placebo was -49.28% (95.0% CI: -59.02 to -39.54, p-value 0.0001), and for Olezarsen 80 mg vs placebo was -53.15% (95.0% CI: -62.92 to -43.38, p-value 0.0001).
- At Month 12, the least squares mean percent change from baseline in fasting TG was -5.59% for placebo, -51.67% for Olezarsen 50 mg, and -60.39% for Olezarsen 80 mg. The least squares mean difference for Olezarsen 50 mg vs placebo was -46.07% (95.0% CI: -55.71 to -36.43, p-value 0.0001), and for Olezarsen 80 mg vs placebo was -54.8% (95.0% CI: -64.46 to -45.13, p-value 0.0001).
Regarding the proportion of participants who achieved fasting TG levels below 150 mg/dL (with baseline TG <500 mg/dL):
- At Month 6, 11.4% of participants in the placebo group achieved this threshold, compared to 79.2% in the Olezarsen 50 mg group and 84.0% in the Olezarsen 80 mg group. The odds ratio for Olezarsen 50 mg vs placebo was 37.51 (95.0% CI: 10.14 to 138.81, p-value 0.0001), and for Olezarsen 80 mg vs placebo was 62.59 (95.0% CI: 15.48 to 253.07, p-value 0.0001).
- At Month 12, 5.7% of participants in the placebo group achieved this threshold, compared to 69.8% in the Olezarsen 50 mg group and 82.0% in the Olezarsen 80 mg group.
What this means
The results indicate that olezarsen significantly reduces fasting triglyceride levels in patients with hypertriglyceridemia. Both the 50 mg and 80 mg doses demonstrated substantial reductions in TG levels at both 6 and 12 months compared to placebo, with the 80 mg dose showing a slightly greater effect. The high proportion of participants achieving fasting TG levels below 150 mg/dL suggests that olezarsen could be an effective treatment option for managing hypertriglyceridemia and potentially reducing cardiovascular risk in these populations. These findings support further development of olezarsen.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05355402, titled "A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Adults With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (E", were posted on 2026-04-23 on clinicaltrials.gov.