Novartis' inclisiran (Leqvio) has shown clinically meaningful and statistically significant low-density lipoprotein cholesterol (LDL-C) lowering as a monotherapy compared to both placebo and ezetimibe in patients at low or moderate risk of atherosclerotic cardiovascular disease (ASCVD). These topline results come from the Phase III V-MONO study, a randomized, double-blind, placebo- and active comparator-controlled trial.
The V-MONO study randomized 350 patients to receive either inclisiran (n = 174), ezetimibe (n = 89), or placebo (n = 87). The primary endpoints were the percentage change in LDL-C from baseline to day 150 compared with both a placebo and with ezetimibe. This trial marks the first assessment of a small interfering RNA (siRNA) therapy for LDL-C lowering as a monotherapy.
Inclisiran's Mechanism and Administration
Inclisiran is administered via subcutaneous injection by a healthcare provider. The regimen involves an initial dose, a second dose at 3 months, and then subsequent doses every 6 months. This twice-yearly cadence aims to improve patient adherence, a known challenge in long-term cholesterol management.
Expert Commentary
"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,” said Shreeram Aradhye, MD, president, development and chief medical officer, Novartis, in a statement. “This trial adds to the growing body of evidence for [inclisiran] across the full spectrum of ASCVD as we strive to help more patients in need.”
The VictORION Program
V-MONO is part of the VictORION clinical trial program, designed to build upon existing evidence demonstrating inclisiran’s benefits across various patient populations. The program includes randomized clinical trials, implementation research, real-world evidence studies, and primary and secondary prevention trials. To date, VictORION encompasses over 30 trials, enrolling more than 60,000 patients in over 50 countries.
Regulatory Context and Future Plans
Inclisiran was initially approved by the FDA in 2021 for patients already on a maximally tolerated dose of statins who required additional LDL-C reduction. In 2023, the label was expanded to include earlier use among patients with elevated LDL-C and an increased risk of heart disease, as an adjunct to diet and statin therapy. Novartis plans to present the full V-MONO data at an upcoming scientific meeting and share it with regulatory agencies.
