Olezarsen substantially reduces triglyceride levels without significant adverse effects in patients with moderate to extreme hypertriglyceridemia, international studies suggest.
Findings presented at the American College of Cardiology’s Annual Scientific Session indicate that the investigational drug that blocks production of apolipoprotein C-III (apoC3) is a promising option for patients in the face of an unmet clinical need when it comes to triglyceride management.
“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 Professor Brian Bergmark, principal investigator of the BRIDGE-TIMI 73a study.
The phase 2b randomised control trial compared the triglyceride-lowering effects of two doses of olezarsen – a ligand-conjugated antisense oligonucleotide, targeting apolipoprotein C-III (apoC3) messenger RNA – in 154 patients (median age 62 years, 42% women) already receiving the standard-of-care treatment.
Participants were eligible for the trial if they had moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg/dL) and elevated cardiovascular risk or severe hypertriglyceridemia (triglyceride level, ≥500 mg/dL).
They were randomly assigned to receive olezarsen (50 mg or 80 mg) or placebo every four weeks for up to 49 weeks, and followed for one year of treatment.
The study ran across 24 sites in the US and Canada.
Findings published in the New England Journal of Medicine [link here] showed that the 50 mg dose of olezarsen reduced triglyceride levels by 49% and the 80 mg dose reduced triglyceride levels by 53%.
Patients who received the 50 mg dose had an average reduction of 64% in levels of apoC3, while those on the 80 mg dose had an average reduction of 73%.
Levels of apolipoprotein B (apoB) were reduced by about 18% on both doses.
All reductions in lipid levels were maintained for 12 months.
The researchers said clinically significant adverse effects such as abnormalities affecting the kidneys, liver or platelets were uncommon.
Speaking in Atlanta, Professor Bergmark noted that the difference between olezarsen doses was relatively small in terms of the triglyceride-lowering effect.
However, the 80 mg dose resulted in a larger reduction in apoC3 than the 50 mg dose. In addition, the reduction in levels of apoB was of interest since the protein was found on all lipid particles that contribute to cholesterol buildup.
“If you actually want to reduce a patient’s risk for 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,” said Professor Bergmark, from Thrombolysis in Myocardial Infarction Study Group at Brigham and Women’s Hospital and Harvard Medical School.