Olpasiran reduces oxidized phospholipids but not inflammatory markers

Treatment with olpasiran appears to induce a sustained and significant decrease in oxidized phospholipids associated with apolipoprotein B (OxPL-apoB) but exert no substantial effect on high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity interleukin-6 (hs-IL-6), according to data from the phase II, dose-finding OCEAN(a)-DOSE trial.

OCEAN(a)-DOSE included 281 patients (median age 62 years, 31.6 percent female) with atherosclerotic cardiovascular disease and Lp(a) levels >150 nmol/L. These patients were randomly assigned to receive placebo or olpasiran at one of the following doses: 10 mg every 12 weeks (Q12W), 75 mg Q12W, 225 mg Q12W, or 225 mg every 24 weeks (Q24W). Treatment was administered subcutaneously.

The primary outcome was placebo-adjusted change in OxPL-apoB from baseline to week 36. Changes in hs-CRP and hs-IL-6 were also assessed. The median baseline Lp(a) and OxPL-apoB concentration were 260.3 and 26.5 nmol/L, respectively.

Compared with placebo, olpasiran was associated significant reductions in OxPL-apoB at week 36. This was true for all dose groups (10-mg Q12W: −51.6 percent, 95 percent confidence interval [CI], −64.9 to −38.2; 75-mg Q12W: −89.7 percent, 95 percent CI, −103.0 to −76.4; 225-mg Q12W dose: −92.3 percent, 95 percent CI, −105.6 to −78.9; Q24W: −93.7 percent, 95 percent CI, −107.1 to −80.3; p<0.001 for all). These reductions were sustained through week 48 (−50.8 percent, −100.2 percent, −104.7 percent, and −85.8 percent, respectively; p<0.001 for all).

Among olpasiran-treated patients, the reduction in OxPL-apoB concentration correlated with the decrease in Lp(a) concentration (p<0.001).

Olpasiran showed no significant effect on hs-CRP or hs-IL-6 at week 36 or 48 when compared with placebo (p>0.05).