Inclisiran Significantly Lowers LDL-C in V-MONO Study

Twice-yearly inclisiran (Leqvio; Novartis) monotherapy showed superiority to both placebo and ezetimibe, showing clinically meaningful and statistically significant low-density lipoprotein cholesterol (LDL-C) lowering in patients at low or moderate risk of atherosclerotic cardiovascular disease (ASCVD), according to a press release from Novartis.¹

The topline results come from the phase 3 V-MONO study, which met its primary end points of percentage change in LDL-C from baseline to day 150 compared with both a placebo and with ezetimibe. The randomized, double-blind, placebo- and active comparator–controlled study is evaluating inclisiran’s efficacy among individuals with primary hypercholesterolemia at a low or moderate risk of developing ASCVD who are not receiving lipid-lowering therapy.²

In the V-MONO study, 350 patients were randomized to receive either inclisiran (n = 174), ezetimibe, (n = 89) or placebo (n = 87). It is the first trial to assess a small interfering RNA (siRNA) therapy for LDL-C lowering as a monotherapy.¹

Inclisiran's twice-yearly cadence and physician administration have potential to improve adherence to treatment, which is a common challenge with cholesterol management. Image credit: Robert - stock.adobe.com

“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 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.”

V-MONO is part of the VictORION clinical trial program, which aims to build upon foundational evidence showing inclisiran’s benefits across patient populations. VictORION includes randomized clinical trials, implementation research, real-world evidence, and primary and secondary prevention trials. The program encompasses more than 30 trials enrolling more than 60,000 patients in more than 50 countries.

Inclisiran is a subcutaneous injection administered for an initial dose, a dose at 3 months, and then every 6 months by a health care provider. Its twice-yearly cadence and physician administration have potential to improve adherence to treatment, which is a common challenge with cholesterol management.

The full data from V-MONO so far will be presented at an upcoming scientific meeting and shared with regulatory agencies, according to the press release.

Inclisiran was already FDA approved in 2021 for patients already receiving a maximally tolerated dose of statins and in need of additional LDL-C reduction, and an expanded label approval in 2023 broadened its indication to encompass earlier use among patients with elevated LDL-C and an elevated risk of heart disease, as an adjunct to diet and a statin regimen.³

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 30, 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. Efficacy and safety of inclisiran as monotherapy in patients with primary hypercholesterolemia not receiving lipid-lowering therapy. ClinicalTrials.gov. Updated July 11, 2024. Accessed August 30, 2024. https://clinicaltrials.gov/study/NCT05763875

3. PT Staff. FDA expands label for inclisiran to include adults with high LDL-C, increased risk of heart disease. Pharmacy Times^®. July 11, 2023. Accessed August 30, 2024. https://www.pharmacytimes.com/view/fda-expands-label-for-inclisiran-to-include-adults-with-high-ldl-c-increased-risk-of-heart-disease