Table 2.
Emerging targeted Lp(a)-lowering therapies.
| Drug | Mechanism of action | Mean/median Lp(a) reduction (%) | Absolute Lp(a) reduction (nmol/L) | Current clinical trial stage/NCT identifier | Projected trial completion |
|---|---|---|---|---|---|
| Pelacarsen | GalNAc-conjugated ASO targeting apo(a) mRNA | Phase 2: 35–80 % [141] |
Phase 2: 96–188 |
Phase 3 [Lp(a)HORIZON]/ NCT04023552 |
2025 |
| Olpasiran | GalNAc-conjugated siRNA targeting apo(a) mRNA | Phase 2: 70–97 % [143] |
Phase 2: 250 |
Phase 3 [OCEAN(a)-Outcomes] NCT05581303 |
2026 |
| Zerlasiran | GalNAc-conjugated siRNA targeting apo(a) mRNA | Phase 1: 46–98 % [144] |
Phase 1: 183–259 |
Phase 2 NCT05537571 |
2024 |
| Lepodisiran | GalNAc-conjugated siRNA targeting apo(a) mRNA | Phase 1: 41–97 % [161] | Phase 1: 36–127 | Phase 2 NCT05565742 |
2024 |
| Muvalaplin | Small molecule inhibitor targeting Lp(a) | Phase 1: Up to 65 % [146] | Phase 1: N/A | Phase 2 [KRAKEN] NCT05563246 |
2024 |
The minimal Lp(a) level entry criteria for all trials described is ≥75 nmol/L (∼30 mg/dL). Lp(a)HORIZON and OCEAN(a)-Outcomes trials include patients with established ASCVD; KRAKEN and the zerlasiran phase 2 trials involve individuals at high-risk of CVD events. The phase 2 trial with lepodisiran involves healthy individuals with high Lp(a). Apo(a) = apolipoprotein(a); ASO = antisense oligonucleotide; ASCVD = atherosclerotic cardiovascular disease; GalNAc = N-acetyl galactosamine; Lp(a) = lipoprotein(a); mRNA = messenger ribonucleic acid; N/A, not available; siRNA = small interfering RNA.