Solbinsiran: Eli Lilly’s Promising ANGPTL3 Inhibitor for Lipid Management

Solbinsiran is an N-acetylgalactosamine-conjugated small interfering RNA (siRNA) developed by Eli Lilly to inhibit hepatic translation of ANGPTL3 mRNA14.

In a Phase II clinical trial, solbinsiran demonstrated significant reductions in multiple lipid parameters:

ANGPTL3:
89% reduction

Triglycerides:
Up to 70% reduction

LDL cholesterol:
Up to 42% reduction

Non-HDL cholesterol:
Up to 46% reduction

Apolipoprotein B:
Up to 36% reduction14

The drug showed a favorable safety profile, with adverse events mostly mild in severity and similar incidence between solbinsiran and placebo groups14.

Solbinsiran's mechanism of action involves reducing ANGPTL3 levels, which leads to increased lipoprotein lipase and endothelial lipase activity, enhancing clearance of triglyceride-rich lipoproteins and LDL particles1.

The drug's effects were sustained at higher doses, suggesting the potential for infrequent dosing1.

Nuclear magnetic resonance lipoprotein analysis showed reductions in the total number of triglyceride-rich lipoprotein and LDL particles with solbinsiran treatment4.

While the impact on cardiovascular outcomes remains to be determined, the broad lipid-lowering effects of solbinsiran make it a promising candidate for treating mixed dyslipidemia17.

Sources:

1. https://www.jacc.org/doi/10.1016/j.jacc.2025.03.005

4. https://www.jacc.org/doi/abs/10.1016/j.jacc.2025.03.005

7. https://www.hcplive.com/view/solbinsiran-significantly-reduces-apob-in-mixed-dyslipidemia-in-phase-2-trial