Olezarsen reduces triglyceride levels in adults with hypertriglyceridemia

Monthly administration of olezarsen 50 or 80 mg significantly reduced triglyceride levels in patients with predominantly moderate hypertriglyceridaemia (HTG) and elevated cardiovascular (CV) risk, according to the Bridge-TIMI 73a trial presented at ACC.24.

At 6 months, olezarsen significantly reduced triglyceride levels by 49.3 percent in the 50-mg cohort and 53.1 percent in the 80-mg cohort compared with placebo (p<0.0001 for both). [ACC.24, LBCT II]

“Both doses of olezarsen resulted in rapid and sustained reductions in triglyceride levels … [and this effect was even] greater than is possible with currently available treatments,” said lead author Dr Brian Bergmark from Brigham and Women’s Hospital, Harvard Medical School in Boston, Massachusetts, US.

This phase IIb trial analysed 154 patients (median age 62 years, 42 percent female) with moderate HTG (triglyceride level 150 to <500 mg/dL) and elevated CV risk or severe HTG (triglyceride level ≥500 mg/dL) who had a median triglyceride level of 242 mg/dL at baseline. Participants were randomized to receive subcutaneous olezarsen 50 mg (n=58) or 80 mg (n=57) or placebo (n=39) once every 4 weeks for up to 49 weeks. Approximately 97 percent of participants received lipid-lowering treatment.

Of the 128 participants who had moderate HTG at baseline, significantly more olezarsen recipients achieved triglyceride levels >150 mg/dL at 6 months than the placebo recipients (85.7 percent [50-mg cohort] and 93.3 percent [80-mg cohort] vs 11.8 percent; p<0.001 for both).

“Of note, the effect of olezarsen on triglyceride levels was evident as soon as 1 month after the initiation of treatment and persisted through 12-month follow-up,” the researchers said. [N Engl J Med 2024;doi:10.1056/NEJMoa2402309]

In terms of other lipid parameters, apolipoprotein C-III, a genetically validated target for lowering triglycerides, was significantly reduced by 64.2 percent and 73.2 percent with olezarsen 50 and 80 mg, respectively, compared with placebo (p<0.0001).

Significant reductions in VLDL-C* (-46.2 percent [50 mg] and -49.7 percent [80 mg]; p<0.0001 for both) and remnant cholesterol (-46.6 percent [50 mg] and -50.1 percent [80 mg]; p<0.0001 for both) were also seen with both olezarsen doses than with placebo.

Similarly, levels of apolipoprotein B (ApoB) and non-high-density lipoprotein-cholesterol (non-HDL-C) were significantly reduced with olezarsen compared with placebo (-18.2 percent [50 mg] and -18.5 percent [80 mg], respectively; p<0.0001 for both).

“If you want to reduce a patient’s risk of a heart attack or stroke, you would like to see a reduction in ApoB, and we did see that in this study, which is very encouraging,” Bergmark said.

In terms of safety, the rates of treatment-emergent adverse events (TEAEs) were similar between the olezarsen and placebo arms, as were the rate of serious AEs, said Bergmark.

“Based on our study’s results, we can say that the drug worked and appeared to be safe. We tested two doses of olezarsen, and both reduced triglyceride levels equally well,” said Bergmark.

“Additionally, olezarsen led to meaningful reductions in ApoB and non-HDL-C, markers of atherogenic risk,” he added.