Pelacarsen lowers lipoprotein(a), corrected LDL cholesterol

The investigational antisense medicine pelacarsen substantially reduces direct lipoprotein(a) cholesterol (Lp[a]-C) and delivers neutral-to-mild lowering of low-density lipoprotein cholesterol (LDL-C) corrected for its Lp(a)-C content (LDL-C_corr), reports a study.

Moreover, LDL-C_corr more accurately reflects the changes in LDL-C than either laboratory-reported LDL-C or the Dahlén formula among patients with elevated Lp(a).

In this study, the researchers assessed patients with a history of cardiovascular disease and elevated Lp(a) who were randomly assigned to five groups of cumulative monthly doses of 20‒80-mg pelacarsen relative to placebo. They measured direct Lp(a)-C on isolated Lp(a) using LPA4-magnetic beads directed to apolipoprotein(a).

LDL-C was reported as follows: LDL-C informed by the clinical laboratory; LDL-C_corr = laboratory-reported LDL-C − direct Lp(a)-C; and LDL-C_corrDahlén = laboratory LDL-C − [Lp(a) mass × 0.30] estimated by the Dahlén formula.

Both groups had baseline median Lp(a)-C values ranging from 11.9 to 15.6 mg/dL. Pelacarsen led to dose-dependent reductions in Lp(a)-C (2 percent vs ‒29 percent to ‒67 percent; p=0.001 to p<0.0001) relative to placebo.

Baseline laboratory-reported mean LDL-C ranged from 68.5 to 89.5 mg/dL, while LDL-C_corr ranged from 55 to 74 mg/dL. Pelacarsen brought about mean percent/absolute changes of ‒2 percent to ‒19 percent/‒0.7 to ‒8.0 mg/dL (p=0.95‒0.05) in LDL-C_corr, ‒7 percent to ‒26 percent/‒5.4 to ‒9.4 mg/dL (p=0.44 to p<0.0001) in laboratory-reported LDL-C, and increases of 3.1 percent to 28.3 percent/0.1‒9.5 mg/dL (p=0.006 to p=0.50) in LDL-C_corrDahlén.

Moreover, total apoB decreased by 3 percent to 16 percent (p=0.40 to p<0.0001), whereas non-Lp(a) apoB did not change significantly.