Olpasiran reduced levels of oxidized phospholipids and lipoprotein(a): JAMA

(1) 10 mg given every 12 weeks (Q12W);

(2) 75 mg given every 12 weeks (Q12W);

(3) 225 mg given every 12 weeks (Q12W); or

(4) 225 mg given every 24 weeks (Q24W).

hs-CRP, hs-IL-6, and OxPL on apolipoprotein B (OxPL-apoB) were measured in 272 patients at baseline, week 36, and week 48. The main result was the change in OxPL-apoB from baseline to week 36, corrected for placebo.

Nearly, 86 individuals (31.6%) were female, and the median (IQR) age of the 272 participants was 62 years (56-69). The initial median (IQR) concentrations of Lp(a) and OxPL-apoB were 260.3 nmol/L (198.1-352.4) and 26.5 nmol/L (19.7-33.9), respectively.

For the 10-mg Q12W dosage, the placebo-adjusted mean percentage change in OxPL-apoB from baseline to week 36 was -51.6%; for the 75-mg Q12W dose, it was -89.7%; for the 225-mg Q12W dose, it was -92.3%; and for the Q24W dose, it was -93.7%.

These results persisted till week 48. For patients receiving olpasiran, there was a significant association between the percentage decrease in Lp(a) and OxPL-apoB. When compared to a placebo at weeks 36 or 48, olapsiran had no discernible effect on hs-CRP or hs-IL-6 (P >.05). Overall, Olpasiran significantly and sustainably decreased OxPL-apoB in the OCEAN(a)-DOSE multicenter randomized clinical study but had no discernible impact on hs-CRP or hs-IL-6.

Source:

Rosenson, R. S., López, J. A. G., Gaudet, D., Baum, S. J., Stout, E., Lepor, N. E., Park, J.-G., Murphy, S. A., Knusel, B., Wang, J., Wilmanski, T., Wang, H., Wu, Y., Kassahun, H., Sabatine, M. S., O’Donoghue, M. L., & OCEAN(a)-DOSE Trial Investigators. (2025). Olpasiran, oxidized phospholipids, and systemic inflammatory biomarkers: Results from the OCEAN(a)-DOSE trial. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2024.5433