• 03 Sep 2025
• Admin
• News Article

Novartis’ Leqvio Hits Key Targets in Phase IV V-DIFFERENCE Study

Novartis announced positive results from V-DIFFERENCE, a phase IV trial evaluating Leqvio (inclisiran) plus lipid-lowering therapy (LLT) versus placebo plus LLT in patients with high cholesterol who had not achieved guideline-recommended LDL-C goals. Findings were presented in a Hot Line session at the 2025 European Society of Cardiology (ESC) Congress in Madrid.

Key Findings

• Primary Endpoint Achieved:
  - After 90 days, 85% of patients on Leqvio + LLT reached LDL-C targets vs 31% on placebo + LLT (p<0.0001).
  - Benefits seen as early as 30 days (81% achieved LDL-C goals).
• LDL-C Reduction:
  - At 360 days, Leqvio reduced LDL-C by an average of 59%, outperforming placebo by 35% (p<0.0001).
  - Clinically significant results observed by day 60.
• Muscle-Related Safety Outcomes:
  - Leqvio patients were 43% less likely to experience muscle-related adverse events (MRAE) (p<0.0001).
  - Numerical improvements reported in pain-related quality-of-life scores.
• Consistency Across Groups:
  • Results held across age, sex, and cardiovascular risk subgroups.

Expert Perspectives

Prof. Ulf Landmesser, M.D. (Charité, Berlin):

“V-DIFFERENCE is the largest LDL-C lowering study with Leqvio to date. These findings highlight effective options for patients still above recommended LDL-C levels.”

Dr. Ruchira Glaser, Novartis:

“The results show Leqvio can help patients reach LDL-C goals faster without additional therapies or maximized statin dosing, transforming cardiovascular care.”

About V-DIFFERENCE (NCT05192941)

• Design: Randomized, double-blind, placebo-controlled.
• Population: 1,770 patients with hypercholesterolemia at high/very high CV risk, randomized 1:1 to Leqvio + LLT (n=898) or placebo + LLT (n=872).
• Endpoints:
  - Primary: Proportion achieving LDL-C target (<55 mg/dL or <70 mg/dL by risk category) at 90 days.
  - Secondary: % change in LDL-C, MRAE occurrence, pain-related QoL (SF-BPI).

Leqvio at a Glance

• Mechanism: First and only siRNA therapy to lower LDL-C.
• Dosing: Subcutaneous injection—initial, 3 months, then every 6 months.
• Adherence Advantage: HCP-administered, twice-yearly dosing helps overcome compliance issues.
• Global Reach: Approved in 100+ countries, licensed from Alnylam Pharmaceuticals.

The Bigger Picture – VictORION Program

• Encompasses 60,000+ patients across 50 countries.
• Includes trials such as ORION-4 (secondary prevention), V-2-PREVENT, V-1-PREVENT, V-INTERVENTION, V-PLAQUE, and V-RIDES.
• Focuses on randomized clinical trials, real-world data, prevention studies, and patient-centered outcomes.

The Unmet Need in Cardiovascular Health

• Cardiovascular disease (CVD): Leading global killer, responsible for more deaths than cancer, diabetes, or lung disease combined.
• Atherosclerotic cardiovascular disease (ASCVD): Causes 85% of CV deaths; primary cause of mortality in the EU and U.S.
• LDL-C exposure: Key driver of atherosclerotic plaque build-up, heart attack, and stroke risk.
• Prevention Opportunity: Lowering LDL-C by 10 mg/dL can cut major CV event risk by ~20%.