Leqvio Achieves Statistically Significant LDL-C Lowering in Phase III Study
The Phase III V-MONO clinical trial met its primary endpoints, demonstrating Leqvio (inclisiran) monotherapy as superior to placebo and ezetimibe.
Novartis has shared positive results from its Phase III study of Leqvio (inclisiran) in patients who were at low or moderate risk of developing atherosclerotic cardiovascular disease (ASCVD) and not receiving lipid-lowering therapy. The trial met its primary endpoints, showing inclisiran achieved clinically meaningful and statistically significant low-density lipoprotein cholesterol (LDL-C) lowering versus both placebo and ezetimibe.1
The Phase III study, V-MONO (NCT05763875), is part of the VictORION program assessing inclisiran for primary and secondary ASCVD prevention. V-MONO is a randomized, double-blind, placebo- and active-comparator controlled trial. It enrolled 350 patients, who were randomized in a 2:1:1 ratio to inclisiran, ezetimibe, or placebo over six months. The study’s primary endpoints were the percent change in LDL-C from baseline to Day 150.
“We are proud that we continue to advance 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,” Shreeram Aradhye, MD, president, development and chief medical officer, Novartis said in a press release. “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.”
VictORION has enrolled over 60,000 patients in more than 50 countries. It has given participants access to over 30 trials worldwide including ORION-4 (secondary prevention), V-2-PREVENT (secondary prevention), V-1-PREVENT (high-risk primary prevention), V-INCEPTION, and V-INCLUSION.
Last August, Novartis shared results from the Phase III ORION-8 study (NCT03814187) which evaluated the efficacy of inclisiran beyond six years. In addition to statin therapy, it demonstrated consistent LDL-C reduction beyond the six-year mark.2
“These long-term results show that twice-yearly inclisiran, when used in addition to statin therapy, provides consistent LDL-C reduction in patients with ASCVD, and those at increased risk of developing cardiovascular disease,” Norman Lepor, MD, Los Angeles-based cardiologist and director of the National Heart Institute said in a press release from the time. “While LDL-C is one of the most readily modifiable risk factors for heart disease, many patients do not reach their recommended LDL-C target through use of statin therapy alone. The demonstrated long-term efficacy of inclisiran indicates that after administration by a health care provider (HCP), both patient and HCP can be confident that a dose has been received for six months.”
David Soergel, MD, global head of cardiovascular, renal and metabolic drug development, Novartis added, “The ORION-8 results affirm the benefits of Leqvio in helping patients achieve sustained LDL-C reduction, which is important as cumulative exposure to LDL-C leads to the growth of plaque in the arteries and an increased risk of cardiovascular events. The trial is part of a growing body of evidence for Leqvio being generated through our ongoing VictORION program that is examining the use of Leqvio in broad and varied patient populations affected by ASCVD.”
According to Novartis, inclisiran remains the first and only small interfering RNA therapy to lower LDL-C.
References
1. Novartis twice-yearly* Leqvio® demonstrated clinically meaningful, statistically significant LDL-C lowering as a monotherapy in patients at low or moderate ASCVD risk. News release. Novartis. August 28, 2024. Accessed August 29, 2024. https://www.novartis.com/news/media-releases/novartis-twice-yearly-leqvio-demonstrated-clinically-meaningful-statistically-significant-ldl-c-lowering-monotherapy-patients-low-or-moderate-ascvd-risk
2. Novartis presents new long-term Leqvio® (inclisiran) data demonstrating consistent efficacy and safety beyond six years. News release. Novartis. August 28, 2023. Accessed August 29, 2024. https://www.novartis.com/news/media-releases/novartis-presents-new-long-term-leqvio-inclisiran-data-demonstrating-consistent-efficacy-and-safety-beyond-six-years
Unifying Industry to Better Understand GCP Guidance
May 7th 2025In this episode of the Applied Clinical Trials Podcast, David Nickerson, head of clinical quality management at EMD Serono; and Arlene Lee, director of product management, data quality & risk management solutions at Medidata, discuss the newest ICH E6(R3) GCP guidelines as well as how TransCelerate and ACRO have partnered to help stakeholders better acclimate to these guidelines.
