Leqvio (inclisiran) shows statistically significant and clinically meaningful early LDL-C goal achievement with less muscle pain – Novartis

Novartis 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 were presented at 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 first 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.”

About V-DIFFERENCE
V-DIFFERENCE (NCT05192941) is a randomized, double-blind, placebo-controlled Phase IV study to evaluate the efficacy, safety, and quality-of-life (QoL) outcomes of Leqvio compared to placebo, on top of individually optimized lipid-lowering therapy (LLT), in individuals with high cholesterol (hypercholesterolemia) at high and very high cardiovascular risk who have not achieved guideline-recommended LDL-C goals. A total of 1,770 individuals were randomized in a 1:1 ratio to receive Leqvio plus LLT (n=898) or placebo plus LLT (n=872).

The primary endpoint was the proportion of patients achieving their individual LDL-C target (<55 mg/dL or <70 mg/dL, depending on the cardiovascular risk category) after 90 days of treatment. Key secondary endpoints included the percentage change from baseline in mean LDL-C level, and the proportion of patients experiencing at least one muscle-related adverse event (MRAE) after 360 days of treatment. Other secondary endpoints included the proportion of patients experiencing self-reported pain, and pain-related QoL measures using the Short-Form Brief Pain Inventory (SF-BPI) after 360 days of treatment.

About VictORION
The V-DIFFERENCE study is part of VictORION, a clinical trial program to expand the foundational evidence of LDL-C reduction with Leqvio in diverse patient populations through randomized clinical trials, implementation research, real-world evidence, and primary and secondary prevention trials assessing the potential benefits of Leqvio on cardiovascular outcomes. The VictORION program is one of the largest clinical trial programs of its kind, enrolling over 60,000 patients in more than 50 countries worldwide across more than 30 trials, including ORION-4 (secondary prevention), V-2-PREVENT (secondary prevention), V-1-PREVENT (high-risk primary prevention), V-INTERVENTION, V-PLAQUE, and V-RIDES.