Novartis has announced encouraging results from its Phase IV V-DIFFERENCE study, which evaluated Leqvio (inclisiran) in patients with high cholesterol who had not met guideline-recommended LDL-C (low-density lipoprotein cholesterol) targets despite being on optimized lipid-lowering therapy (LLT). The study compared Leqvio to placebo, with both treatments given in addition to existing LLT regimens. These results will be presented at a Hot Line session during the 2025 European Society of Cardiology (ESC) Congress in Madrid, running from August 29 to September 1.
The study showed that after 90 days of treatment with Leqvio, 85% of patients achieved their LDL-C goals, compared to just 31% of those receiving placebo (p<0.0001). Benefits emerged as early as 30 days into treatment, with 81% of Leqvio-treated patients reaching their LDL-C targets. These improvements were observed across all age groups, sexes, and cardiovascular risk categories. The findings further strengthen the clinical profile of Leqvio as part of the broader VictORION program, which includes over 60,000 patients across 50 countries.
Dr. Ulf Landmesser, Chairman of the Department of Cardiology, Angiology and Intensive Care Medicine at the German Heart Center of Charité and Charité University Medicine Berlin, emphasized the significance of the study. “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,” he said. “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.”
The V-DIFFERENCE trial is also the first to assess Leqvio’s effect on muscle symptoms and pain—common concerns among patients taking statins and other LLTs. Patients receiving Leqvio plus LLT were 43% less likely to experience muscle-related adverse events compared to those on placebo plus LLT (p<0.0001), and improvements were also reported in pain-related quality-of-life scores. Over the course of 360 days, Leqvio reduced LDL-C levels by an average of 59%, outperforming placebo plus LLT by 35% (p<0.0001), with meaningful differences noted as early as 60 days into treatment.
Dr. Ruchira Glaser, Global Head of the Cardiovascular, Renal, and Metabolic Development Unit at Novartis, highlighted the broader implications of the findings. “Novartis is dedicated to tackling the most challenging problems in cardiovascular disease,” she said. “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.”
With cardiovascular disease remaining a leading global health concern, the V-DIFFERENCE results reinforce Leqvio’s potential to play a central role in managing high cholesterol, especially for patients who struggle to achieve LDL-C goals through conventional therapies.