Novartis' biannual Leqvio® significantly lowers LDL-C in low/moderate ASCVD risk patients

BASEL, Switzerland, August 28, 2024 – Novartis has announced positive topline results from the Phase III V-MONO study evaluating Leqvio® (inclisiran) as a monotherapy. The trial met its primary endpoints by demonstrating clinically significant and statistically meaningful reductions in low-density lipoprotein cholesterol (LDL-C) compared to both placebo and ezetimibe. This study focused on patients at low or moderate risk of developing atherosclerotic cardiovascular disease (ASCVD) who were not on any lipid-lowering therapy.

V-MONO is notable for being the first study to assess a small interfering RNA (siRNA) therapy, administered as a monotherapy, aimed at lowering LDL-C in patients with a lower risk of ASCVD. Novartis plans to present the detailed results at an upcoming medical meeting and will share the findings with regulatory bodies, including the US Food and Drug Administration (FDA).

Shreeram Aradhye, M.D., President of Development and Chief Medical Officer at Novartis, stated, "We are proud to continue advancing the scientific understanding of using siRNA therapy to tackle one of the world’s biggest healthcare challenges, as too many people still struggle to reach their cholesterol goals. This trial adds to the growing body of evidence for Leqvio across the full spectrum of ASCVD as we strive to help more patients in need.”

Continuing their efforts, Novartis is conducting multiple studies to evaluate the potential uses of Leqvio across both primary and secondary prevention contexts. The VICTORION-1-PREVENT (V1P) study is singular in its scope, as it focuses on a non-statin lipid-lowering therapy within a high-risk primary prevention population, as defined by the American College of Cardiology (ACC) and American Heart Association (AHA) guidelines. This study is on track to complete enrollment later this year. Additionally, in the secondary prevention setting, the ORION-4 and VICTORION-2-PREVENT (V2P) outcome studies are expected to provide data by 2026 and 2027, respectively.

The V-MONO study (CKJX839D12304) itself was a six-month, randomized, double-blind, placebo- and active-comparator controlled Phase III trial. It evaluated the efficacy of Leqvio as a monotherapy in patients at low or moderate risk of developing ASCVD who were not receiving any lipid-lowering therapies. A total of 350 patients were enrolled and randomly assigned in a 2:1:1 ratio to receive inclisiran, ezetimibe, or a placebo. The primary outcomes measured were the percentage change in LDL-C from baseline to Day 150 when using Leqvio compared to the placebo and ezetimibe groups.

This study is part of a broader clinical trial program known as VictORION, which seeks to expand foundational evidence on LDL-C reduction with Leqvio across diverse patient populations. VictORION includes a variety of randomized clinical trials, implementation research, real-world evidence, and both primary and secondary prevention trials to evaluate the potential cardiovascular benefits of Leqvio. This extensive program is one of the largest of its kind, aiming to enroll over 60,000 patients from more than 50 countries worldwide in over 30 different trials, including ORION-4, V-2-PREVENT, V-1-PREVENT, V-INCEPTION, and V-INCLUSION.

Leqvio represents a pioneering approach in cholesterol management as the first and only siRNA therapy aimed at lowering LDL-C. Administered via subcutaneous injection by a healthcare provider, it requires an initial dose, a follow-up dose after three months, and subsequent doses every six months. This biannual administration may help address the common challenge of treatment adherence in cholesterol management. Leqvio has been approved in nearly 100 countries, including the United States, European Union, Japan, and China. Novartis developed Leqvio in collaboration with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide, contributing to 85% of all cardiovascular deaths. The disease is driven by the accumulation of low-density lipoprotein cholesterol (LDL-C) in artery walls, leading to plaque formation that can result in heart attacks or strokes. Addressing and managing LDL-C levels is critical in preventing premature cardiovascular deaths, which comprise a significant portion of global health challenges.

Novartis remains committed to pioneering the next generation of cardiovascular treatments, focusing on areas such as hypertension, hyperlipidemia, and heart failure. Through continuous innovation and collaboration with healthcare professionals and patients, Novartis aims to improve cardiovascular care and help people live longer, healthier lives.