In Brief | Cardiovascular Disease
Efficacy and Safety of Solbinsiran in Mixed Dyslipidaemia: Phase 2 Trial Findings
Time to read: 02:23
Time to listen: 04:18
Originally Published: 3 May 2025
Source: Lancet
Type of article: In Brief
MedED Catalogue Reference: MCIB009
Category: Cardiovascular Disease
Cross Reference: Gerontology
Keywords: cardiovascular diseases, hyperlipidemia, ANGPTL3,triglycerides, LDL
Key Takeaway
This article is a review of recent studies originally published in the Lancet, 3 May 2025. This article does not represent the original research, nor is it intended to replace the original research. Access the full Disclaimer Information.
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Mixed dyslipidaemia, characterised by elevated triglycerides and LDL cholesterol (LDL-C), is a key contributor to atherosclerotic cardiovascular disease. Therapeutic targeting of angiopoietin-like protein 3 (ANGPTL3)—a regulator of lipoprotein metabolism—has emerged as a potential intervention point.
Solbinsiran, a GalNAc-conjugated small interfering RNA (siRNA) molecule targeting hepatic ANGPTL3, has previously shown lipid-lowering potential in early-phase research.
Study Purpose
This phase 2 trial, published in the Lancet, aimed to evaluate the efficacy, durability, and safety of solbinsiran in reducing atherogenic lipoproteins, including apolipoprotein B (apoB), in adults with mixed dyslipidaemia already receiving moderate- to high-intensity statin therapy.
ClinicalTrials.gov NCT05256654
Study Methodology
This was a double-blind, placebo-controlled, randomised phase 2 study conducted across 41 sites in seven countries.
Adults (≥18 years) with fasting triglyceride levels between 1.69–5.64 mmol/L, LDL-C ≥1.81 mmol/L, and non–HDL-C ≥3.36 mmol/L were enrolled.
Participants (n=205) were randomly assigned to receive solbinsiran 100 mg (n=30), 400 mg (n=58), or 800 mg (n=59), or placebo (n=58), via subcutaneous injection on days 0 and 90. Follow-up continued through to day 270.
The primary endpoint was percentage change in apoB concentration from baseline to day 180 in the efficacy population.
Findings
205 patients were randomised (median age 57 years, 54% female).
Only the 400 mg dose significantly reduced apoB levels by 14.3% versus placebo (p=0.0085).
This dose also reduced non–HDL-C (–25.5%), LDL-C (–16.8%), triglycerides (–50.3%), VLDL-C (–50.1%), and hepatic fat fraction (–27.6%), while HDL-C was reduced by –16.4%.
The 100 mg dose did not significantly reduce apoB, LDL-C, or non-HDL-C.
The 800 mg dose achieved similar reductions in ANGPTL3 and other lipid fractions to the 400 mg dose but did not significantly reduce apoB at day 180.
Treatment was well tolerated with low rates of adverse events and minimal liver enzyme elevations.
Conclusion
Solbinsiran 400 mg achieved significant reductions in multiple atherogenic lipoproteins and hepatic fat content, with an acceptable safety profile. These findings support further clinical development of solbinsiran in patients with mixed dyslipidaemia at elevated cardiovascular risk.
Study Funding
This study was funded by Eli Lilly & Company
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