Leqvio Demonstrates Significant LDL-C Reduction in Patients at Risk of Atherosclerotic Cardiovascular Disease

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Results from the Phase III V-MONO trial found that Novartis’ Leqvio (inclisiran) demonstrated noteworthy LDL-C reduction as a monotherapy in patients at low to moderate risk of atherosclerotic cardiovascular disease (ASCVD). According to the company, this is the first study to evaluate a small interfering RNA (siRNA) therapy for LDL-C reduction in this patient population. Additionally, results indicated that twice-yearly Leqvio achieved clinically meaningful and statistically significant LDL-C lowering compared to both placebo and ezetimibe in patients not on other lipid-lowering therapies.¹

“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, chief medical officer, Novartis, 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.”

V-MONO is a six-month randomized, double-blind, placebo- and active-comparator controlled study. Investigators enrolled 350 patients who were randomly assigned in a 2:1:1 ratio to receive inclisiran (n=174), ezetimibe (n=89), or placebo (n=87). The primary endpoints of the study were the percent change in LDL-C from baseline to day 150 with Leqvio versus placebo and ezetimibe.

V-MONO itself is a part of VictORION, which is a clinical trial program seeking to expand the foundational evidence of LDL-C reduction with Leqvio in diverse patient populations through randomized clinical trials, implementation research, real-world evidence, and primary and secondary prevention trials assessing the potential benefits of Leqvio on cardiovascular outcomes. According to Novartis, the program has enrolled over 60,000 patients in more than 50 countries in 30 trials, including ORION-4, V-2-PREVENT, V-1-PREVENT, V-INCEPTION, and V-INCLUSION.

Novartis states that ASCVD accounts for nearly 85% of all CV deaths, making it the leading cause of death currently in the EU. In the United States, its burden is more significant than any other chronic diseases.¹ According to the World Health Organization, cardiovascular diseases are the leading cause of death globally, with an estimated 17.9 million mortalities. Further, more than four out of five cardiovascular-related deaths are due to heart attacks and strokes, and one-third of these deaths occur prematurely in people under 70 years of age.²

According to a study published by the American Heart Association, by 2050, the rate of heart failure is expected to jump from 2.7% to 3.8%, coronary disease from 7.8% to 9.2%, strokes from 3.9% to 6.4%, and total cardiovascular disease from 11.3% to 15%. Overall, cardiovascular diseases are expected to affect 45 million adults. Individuals who additionally suffer from hypertension will account for 184 million adults by 2050.³

“The prevalence of many cardiovascular risk factors and cardiovascular and cerebrovascular diseases will increase markedly over the next 30 years, absent interventions to change these trajectories,” report the study authors. “There are deep inequities among people who identify as Black, Hispanic, AI/AN, or multiracial in prevalence and in outcomes of disease that warrant targeted and sustained intervention. The aging of the population will require attention to workforce and to new approaches to care delivery to ensure adequate capacity to provide high-quality cardiovascular care. Clinical and public health interventions are urgently needed to effectively manage, stem, and even reverse these adverse trends in CVD and stroke and should be a priority on the national level.”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. Novartis. August 28, 2024. Accessed August 28, 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. Cardiovascular diseases. WHO. Accessed August 28, 2024. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1

3. Forecasting the Burden of Cardiovascular Disease and Stroke in the United States Through 2050—Prevalence of Risk Factors and Disease: A Presidential Advisory From the American Heart Association. AHA. June 4, 2024. Accessed August 28, 2024. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001256#:~:text=Prevalences%20of%20coronary%20disease%20(7.8,multiracial%2C%20Black%2C%20or%20Hispanic.