Effect of ANGPTL3 Inhibition With Solbinsiran in Preclinical and Early Human Studies
Authors' conclusion
Solbinsiran inhibits hepatic ANGPTL3 translation and results in significant reductions in all atherogenic lipoproteins in mixed dyslipidemia.
Study context
- Population
- Participants with mixed dyslipidemia; mouse and nonhuman primate models
- Comparison
- Solbinsiran vs placebo
Methodological detailssingle-ascending-dose, repeat-dose, Evaluated over 169 days
- Single-ascending-dose
- Repeat-dose
- Evaluated over 169 days
Primary result
As reported in the abstract
Mean % reductions from baseline, single dose (humans)
- ANGPTL3 reduction up to
- 86% ± 4%
- Triglycerides reduction up to
- 73% ± 7%
- LDL-C reduction up to
- 30% ± 16%
- Non-HDL-C reduction up to
- 41% ± 12%
- Apolipoprotein B reduction up to
- 30% ± 11%
Further findings
Repeat-dose study, reductions
- ANGPTL3
- 89% ± 6%
- Triglycerides up to
- 70% ± 13%
- LDL-C up to
- 42% ± 14%
- Non-HDL-C up to
- 46% ± 14%
- Apolipoprotein B up to
- 36% ± 13%
- P < 0.0001 for all
Preclinical ANGPTL3 expression
- Mice: hepatocyte ANGPTL3 messenger RNA (mRNA) reduction vs vehicle
- 65%
- Monkeys: hepatic ANGPTL3 mRNA reduction up to (mean ± SEM)
- 73% ± 2% (P < 0.0001)
- Monkeys: serum ANGPTL3 protein reduction up to (mean ± SEM)
- 69% ± 4% (P < 0.001)
NMR lipoprotein analysis
- Reductions in total number of triglyceride-rich lipoprotein and low-density lipoprotein (LDL) particles with solbinsiran
Safety
Adverse events
- Mostly mild; similar incidence with solbinsiran and placebo
Original publication
Effect of ANGPTL3 Inhibition With Solbinsiran in Preclinical and Early Human Studies. J Am Coll Cardiol. Published 30 March 2025. doi:10.
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