TABLE 4.
Lipid-Lowering Efficacy of ANGPLT3 Inhibitors
| Therapy | Trial Phase (Ref. #) | Sample Size | Study Design | Dose | TG | Non-HDL-C | Remnant Cholesterol | LDL-C | Total ApoB | ApoB100 | ApoB48 | Apo C-III | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Evinacumab | HTG | 1 (59) | 83 | Single dose Cohort A: (TGs ≥150 and >450 mg/dL) |
5 mg/kg IV | −80.3% (Day 4) | −30.6% (Day 4) | — | −18.2% (Day 8) | −24.6% (Day 4) | — | — | — |
| 10 mg/kg IV | −88.0% (Day 4) | −31.2% (Day 11) | — | −19.0% (Day 4) −22.8% (Day 8) −14.5% (Day 22) |
−21.4% (Day 11) | — | — | — | |||||
| 20 mg/kg IV | −83.9% (Day 4) | −35.4% (Day 11) | — | −16.3% (Day 4) −14.8% (Day 43) |
−26.8% (Day 11) | — | — | — | |||||
| 75 mg SC | −20.8% (Day 4) | −6.9% (Day 43) | — | −12.4% (Day 11) | −3.4% (Day 43) | — | — | — | |||||
| 150 mg SC | −40.8 (Day 4) | −12.9% (Day 4) | — | −12.9% (Day 3) −15.9% (Day 8) |
−8.3% (Day 8) | — | — | — | |||||
| 250 mg SC | −55.5% (Day 4) | −23.7% (Day 11) | — | −20.6% (Day 8) −20.3% (Day 11) |
−13.6% (Day 43) | — | — | — | |||||
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| Evinacumab | HTG | 1 (60) | 16 | Single dose Cohort B: High HTG (≥450 and <1,500 mg/dL) Cohort C: Severe HTG (>1,000 mg/dL) |
10 mg/kg IV [Cohort B] | -81.8% (Day 4) | −32.0 (Day 8) | — | +54.4% (Day 4) | — | — | — | — |
| 20 mg/kg IV [Cohort C] | −0.9 to −93.2% (Day 3) | −57.8 (Day 22) | — | +74.4% (Day 29) | — | — | — | — | |||||
| 250 mg SC [Cohort C] | −37.8% (Day 8) | −27.4 (Day 8) | — | +79.6% (Day 64) | — | — | — | — | |||||
| HTG | 1 (61) | 56 | Multiple ascending dose | 20 mg/kg IV Q4W | −88.2% (Day 2) | −45.8% (Day 36) | — | −25.1% (Day 57) | −30.7% (Day 57) | — | — | — | |
| −39.8% (Day 57) | |||||||||||||
| 150 mg SC QW | −42.0% (Day 57) | −24.5% (Day 57) | — | −12.4% (Day 57) | −17.9% (Day 36) | — | — | — | |||||
| 300 mg SC Q2W | −45.5% (Day 36) | −14.7% (Day 57) | — | −8.6% (Day 8) | −18.5% (Day 36) | — | — | — | |||||
| 300 mg SC QW | −51.9% (Day 15) | −37.5% (Day 57) | — | −22.0% (Day 57) | −23.7% (Day 57) | — | — | — | |||||
| 450 mg SC Q2W | −52.8% (Day 57) | −22.6% (Day 57) | — | −13.1% (Day 8) | −17.8% (Day 57) | — | — | — | |||||
| 450 mg SC QW | −50.3% (Day 15) | −26.2% (Day 57) | — | −12.0% (Day 57) | −17.4% (Day 36) | — | — | — | |||||
| HeFH | 2 (65) | 252 | Double-blind, placebo-controlled. Evinacumab 15 mg/kg IV Q4W. 2:1 randomization (Exclusion criteria: TG >400 mg/dL and >300 mg/dL for patients without and with history of diabetes mellitus, respectively) | 5 mg/kg Q4W | −25.2% | −23.7% | — | −24.2% | −16.6% | — | — | — | |
| 15 mg/kg Q4W | −45.9% | −50.9% | — | −50.5% | −39.4% | — | — | — | |||||
| 300 mg SC Q2W | −46.l% | −39.3% | — | −38.5% | −26.6% | — | — | — | |||||
| 300 mg SC QW | |||||||||||||
| 450 mg SC QW | −55.8% | −53.8% | — | −52.9% | −42.0% | — | — | — | |||||
| −61.5% | −58.5% | — | −56.0% | −45.5% | — | — | — | ||||||
| HoFH | 3(66) | 64 | Double-blind, placebo-controlled Evinacumab 15 mg/kg IV QW. 2:1 randomization (Inclusionc criteria: untreated TG <300 mg/dL) |
15 mg/kg IV | −50.4 | −51.7 | — | −49.0 | −36.9% | — | — | −90.0% | |
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| Vupanorsen | 1 (62) | Single dose | — | — | — | — | — | — | — | — | — | ||
| TG>150 mg/dL, T2DM and hepatic steatosis | 2 (63) | 105 | Double-blind, placebo-controlled. Vupanorsen 80 mg vs. placebo Q4W | — | −53 | −18 | −38 | −7 (NS) | — | −9 (NS) | —— | −58 | |
ANGPTL3 = angiopoietin-like 3; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia; HTG = hypertriglyceridemia; IV = intravenous; NS = not significant; T2DM = type 2 diabetes mellitus; Q2W = every 2 weeks; other abbreviations as in Table 3.