Phase 2 trials showed the antisense oligonucleotide pelacarsen reduced mean Lp(a) levels by 80%, allowing 98% of subjects to reach on-treatment levels of <125 nmol/l.
Does lowering Lp(a) with RNA therapeutics like pelacarsen reduce major adverse cardiovascular events in patients with cardiovascular disease?
RNA therapeutics such as pelacarsen potently lower Lp(a) levels by 80%, setting the stage for ongoing phase 3 trials to definitively test the Lp(a) hypothesis for cardiovascular risk reduction.
Lipoprotein(a) Lp(a) has risen to the level of an accepted cardiovascular disease risk factor, but final proof of causality awaits a randomized trial of Lp(a) lowering. Inhibiting apolipoprotein(a) production in the hepatocyte with ribonucleic acid therapeutics has emerged as an elegant and effective solution to reduce plasma Lp(a) levels. Phase 2 clinical trials have shown that the antisense oligonucleotide pelacarsen reduced mean Lp(a) levels by 80%, allowing 98% of subjects to reach on-treatment levels of 70 mg/dl and >90 mg/dl, in which either of the two being positive will lead to a successful trial. Additional ribonucleic acid-targeted therapies to lower Lp(a) are in preclinical and clinical development. The testing of the Lp(a) hypothesis will provide proof whether Lp(a)-mediated risk can be abolished by potent Lp(a) lowering.
Tsimikas et al. (Mon,) conducted a review in Cardiovascular disease with elevated Lipoprotein(a). Pelacarsen vs. Placebo was evaluated on Major adverse cardiovascular events. Phase 2 trials showed the antisense oligonucleotide pelacarsen reduced mean Lp(a) levels by 80%, allowing 98% of subjects to reach on-treatment levels of <125 nmol/l.
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