Table 1.
LDL-C reduction through different PCSK9 inhibition approaches
| Type of inhibition | LDL-C reduction (%) | Relative CV reduction | Status | References |
|---|---|---|---|---|
| mAbs targeting circulating PCSK9 (evolocumab and alirocumab) | 55–60% | 15–20% | Approved by FDA and EMA | 24 , 28 |
| Gene silencing (siRNA and inclisiran) | 30–50% | Under evaluation in ORION-4 | Phase III | 29 , 30 |
| Gene editing (CRISPR-Cas9) | ∼30% (TC) | – | Preclinical | 31 |
| Inhibition of PCSK9 mRNA translation (PF-06446846) | ∼58% | – | Preclinical (halted) | 32 |
| Adnectins | ∼50% | – | Preclinical (halted) | 33 |
| ABD-fused Anticalin | ∼50–60% | – | Preclinical | 34 |
| mAb against PCSK9 CHRD | ∼40% | – | Preclinical | 35 |
| Single domain antibodies (sdAbs) | ∼50% | – | Preclinical | 36 , 37 |
| Vaccine | 13.3% | – | Phase I | Bauer et al., ESC Congress, 2018 Munich |