Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy.

Summary

CKJX839D12304 was a research study to determine if the study treatment, called inclisiran, in comparison to placebo and ezetimibe effectively reduces Low-Density Lipoprotein Cholesterol (LDL-C) as measured by percentage change from baseline to Day 150. This study was conducted in eligible participants with primary hypercholesterolemia not receiving any lipid-lowering therapy (LLT), with a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%.

Timeline

Start

2023-03-15

Primary completion

2024-06-20

Completion

2024-06-20

Outcome

Met primary endpoint

registry analysis (superiority test); Inclisiran vs Placebo; p <0.0001; LS Mean Difference -47.91 (95% CI -53.62 to -42.20); ANCOVA NCT05763875 ↗

registry analysis (superiority test); Inclisiran vs Ezetimibe; p <0.0001; LS Mean Difference -35.37 (95% CI -40.88 to -29.86); ANCOVA NCT05763875 ↗

paper The difference in the change from baseline with inclisiran vs placebo was -47.9% and vs ezetimibe was -35.4% (both P < 0.0001). PMID 40392667 ↗

release “Phase III V-MONO study met its primary endpoints, demonstrating superiority of Leqvio (inclisiran) monotherapy vs both placebo and ezetimibe in LDL-C reduction” novartis.com ↗

Publications

• Taub PR, Gutierrez A, Wewers D, Garcia Cantu E, Cao H, Deck C, Lesogor A, Ott D, Mena-Madrazo J, Zang X, Wright RS. Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial. J Am Coll Cardiol. 2025 Jul 22;86(3):196-208. doi: 10.1016/j.jacc.2025.04.049. Epub 2025 May 5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Ezetimibe	Unknown	10 mg	Oral
Subject	Inclisiran	Small interfering RNA (siRNA)	284 mg	Subcutaneous

Indications