Olpasiran therapy significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease (ASCVD), based on findings from the OCEAN(a) DOSE trial presented Nov. 6 during AHA 2022 in Chicago and simultaneously published in the New England Journal of Medicine.

Researchers randomly assigned 281 patients to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo. All patients had established ASCVD and the median concentration of lipoprotein(a) at baseline was 260.3 nmol per liter, and the median concentration of LDL cholesterol was 67.5 mg per deciliter. Additionally, 88% of patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a PCSK9 inhibitor at baseline. The primary endpoint was the percent change in the lipoprotein(a) concentration from baseline to week 36.

Results at 36 weeks found a mean 3.6% increase in the lipoprotein(a) concentration in the placebo group, while a substantial reduction in lipoprotein(a) concentration was observed in the olpasiran therapy group based on dose. Researchers noted placebo-adjusted mean percent changes of −70.5% with the 10-mg dose, −97.4% with the 75-mg dose, −101.1% with the 225-mg dose administered every 12 weeks, and −100.5% with the 225-mg dose administered every 24 weeks. The overall incidence of adverse events was similar across both groups. Mild injection site and related hypersensitivity reactions were more common with olpasarin, but these were resolved with treatment.

"These findings set the foundation for phase 3 testing scheduled to commence later this year," said Michelle L. O'Donoghue, MD, MPH, FACC. She added that greater representation of Black and Hispanic/Latinx patients will be important in future trials given their propensity to have higher concentrations of lipoprotein(a).

Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Novel Agents

Keywords: AHA Annual Scientific Sessions, AHA22, RNA, Small Interfering, Drug Tapering, Lipoprotein(a), Apoptosis

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