Novartis Leqvio shows statistically significant, clinically meaningful early LDL-C goal achievement with less muscle pain
Basel: Novartis has announced positive results from V-DIFFERENCE, a Phase IV study evaluating Leqvio (inclisiran) compared to placebo, both administered on top of individually optimized lipid-lowering therapy (LLT), in patients with high cholesterol (hypercholesterolemia) who have not achieved guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. These data will be presented in one of the Hot Line sessions of the 2025 European Society of Cardiology (ESC) Congress, held in Madrid, Spain, from August 29 to September 1, 2025.
After 90 days of treatment with Leqvio on top of LLT, 85% of patients achieved their guideline-recommended LDL-C target compared to 31% of those receiving placebo on top of LLT (p<0.0001). Significant benefits were observed as early as 30 days with 81% of patients achieving LDL-C targets. Results were consistent regardless of age, sex, or cardiovascular risk of trial participants. The results of the V-DIFFERENCE study add to the growing body of evidence for Leqvio within the VictORION clinical program, which encompasses more than 60,000 patients from 50 countries worldwide.
“V-DIFFERENCE is the largest LDL-C lowering study with Leqvio to read out to date, and the first to focus on patient-centered outcomes," said Ulf Landmesser, M.D., Chairman of the Department of Cardiology, Angiology and Intensive Care Medicine at German Heart Center of Charité and Charité University Medicine Berlin. "These findings are significant as they demonstrate effective options for lipid management improvement in patients at risk, a majority of whom continue to remain above recommended LDL-C levels."
V-DIFFERENCE is the study to evaluate the effect of Leqvio on muscle symptoms and pain, which are common amongst patients receiving statins and other LLT. Patients who received Leqvio plus LLT were 43% less likely to experience muscle-related adverse events (MRAE) compared to patients who received placebo plus LLT (p<0.0001), with numerical improvement in pain-related quality-of-life scores also reported. Furthermore, Leqvio on top of LLT reduced LDL-C levels on average by 59% after 360 days of treatment, outperforming placebo plus LLT by 35% (p<0.0001), with clinically significant differences observed as early as 60 days into treatment.
“Novartis is dedicated to tackling the most challenging problems in cardiovascular disease,” said Ruchira Glaser, M.D., Global Head, Cardiovascular, Renal and Metabolic Development Unit, Novartis. “These results highlight the potential of Leqvio to transform cardiovascular care by improving meaningful patient outcomes. V-DIFFERENCE has provided evidence that early use of Leqvio is an effective way to help patients reach their LDL-C goals faster without the need to add other therapies or maximize statin doses.”
Leqvio is approved in more than 100 countries, including the US, EU, Japan and China. Novartis obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.
ASCVD accounts for 85% of all cardiovascular deaths. It is the primary cause of mortality in the European Union and its burden in the US is greater than that of any other chronic diseases. ASCVD is caused by the development and growth of plaques in the inner lining of the arteries. The atherosclerotic plaque is mainly composed of LDL-C that accumulates over time. Cumulative exposure to LDL-C can increase one’s risk of cardiovascular events such as a heart attack or stroke.
