Olpasiran Leads to Significant Reduction in Oxidized Phospholipids

Olpasiran, a small interfering RNA, which blocks lipoprotein(a) (Lp[a]) production, leads to a significant and sustained reduction in oxidized phospholipids (OxPL) on apolipoprotein B (apoB), according to a study published online Feb. 12 in JAMA Cardiology.

Robert S. Rosenson, M.D., from Mount Sinai Hospital in New York City, and colleagues examined the effect of olpasiran on OxPL, high-sensitivity interleukin 6 (hs-IL-6), and high-sensitivity C-reactive protein (hsCRP) in a multicenter, phase 2, dose-finding randomized trial involving 281 patients with atherosclerotic cardiovascular disease and Lp(a) levels >150 nmol/L. Participants were randomly assigned to receive one of four active subcutaneous doses of olpasiran versus placebo: 10 mg every 12 weeks (Q12W); 75 mg Q12W; 225 mg Q12W; or 225 mg every 24 weeks (Q24W).

The researchers found that the placebo-adjusted mean percentage change in OxPL on apoB (OxPL-apoB) concentration from baseline to week 36 was −51.6, −89.7, −92.3, and −93.7 percent for the 10-mg Q12W, 75-mg Q12W, 225-mg Q12W, and 225-mg Q24W doses, respectively, with maintenance of these effects observed to 48 weeks (−50.8, −100.2, −104.7, and −85.8 percent, respectively). For patients treated with olpasiran, there was a strong correlation between percentage reduction in Lp(a) and OxPL-apoB (r = 0.79). No significant impact was seen on hs-CRP or hs-IL-6 for olpasiran versus placebo to weeks 36 or 48.

"Olpasiran leads to a significant reduction in OxPL on apoB," the authors write. "It remains unknown whether these observed effects may offer incremental benefit beyond olpasiran's effect of Lp(a) lowering alone."

Several authors disclosed ties to pharmaceutical companies, including Amgen, which manufactures olpasiran and funded the study.

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