Prevention & lipidsRandomised controlled trial
Effect of ANGPTL3 Inhibition With Solbinsiran in Preclinical and Early Human Studies
- Preclinical and phase 1 randomised placebo-controlled study
- single-ascending-dose
- repeat-dose
- Evaluated over 169 days
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
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:10.1016/j.jacc.2025.03.005
Summarised from the published abstract; every number is checked against it