Novartis’ Leqvio® Demonstrates Statistically Significant And Clinically Meaningful Early LDL-C Goal Achievement With Lower Rates Of Muscle Pain

Novartis announced positive findings from its Phase IV V-DIFFERENCE study, which evaluated Leqvio (inclisiran) compared with placebo. Both treatments were given alongside individually optimized lipid-lowering therapy (LLT) in patients with high cholesterol who had not reached the recommended targets for low-density lipoprotein cholesterol (LDL-C). The results will be presented during a Hot Line session at the European Society of Cardiology (ESC) Congress 2025 in Madrid, Spain.

The study showed that after 90 days of treatment, 85% of patients receiving Leqvio in addition to LLT achieved their guideline-recommended LDL-C goal, compared with only 31% of patients receiving placebo with LLT. Notably, significant improvements were already observed by day 30, with 81% of patients on Leqvio achieving their LDL-C targets. These results were consistent across different age groups, sexes, and cardiovascular risk profiles.

V-DIFFERENCE also explored the effect of Leqvio on muscle symptoms and pain, which are common in patients treated with statins and other LLTs. The study found that patients treated with Leqvio plus LLT were 43% less likely to experience muscle-related adverse events compared to those on placebo plus LLT. Improvements in pain-related quality of life were also reported among patients receiving Leqvio.

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, stated, “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. 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."

Ruchira Glaser, M.D., Global Head, Cardiovascular, Renal and Metabolic Development Unit, Novartis, “Novartis is dedicated to tackling the most challenging problems in cardiovascular disease. 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.”

Over a longer treatment period, Leqvio on top of LLT demonstrated sustained benefits. After 360 days, patients treated with Leqvio achieved an average LDL-C reduction of 59%, which was 35% greater than that seen in the placebo group. Clinically meaningful differences were already evident by day 60 of treatment. The findings from the V-DIFFERENCE trial further support Leqvio’s role in cholesterol management and add to the evidence being generated within the VictORION clinical program, which involves more than 60,000 patients across 50 countries.