Armed with new late-stage data on reducing low-density lipoprotein cholesterol, Novartis is positioning its siRNA therapy Leqvio as a preventive treatment for atherosclerotic cardiovascular disease.
Novartis on Wednesday released topline findings from the Phase III V-MONO study, demonstrating that its siRNA therapy Leqvio (inclisiran) strongly reduced levels of “bad” cholesterol in patients with atherosclerotic cardiovascular disease.
The pharma did not provide specific data in its announcement, only revealing that monotherapy with Leqvio led to a “clinically meaningful and statistically significant” reduction in levels of low-density lipoprotein cholesterol (LDL-C), compared with both placebo and the lipid-lowering drug ezetimibe. Novartis will reveal more details from V-MONO at an upcoming scientific congress.
The company will also share its findings with the FDA with an eye toward expanding Leqvio’s label, potentially opening up preventive use of the therapy.
V-MONO is a randomized and double-blinded study that compared Leqvio versus placebo and the active control ezetimibe. The trial enrolled 350 patients at low or moderate risk of developing atherosclerotic cardiovascular disease (ASCVD) who were not on any lipid-loweing therapies. Its primary efficacy endpoint is the percent change in LDL-C after 150 days.
“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,” Chief Medical Officer Shreeram Aradhye said in a statement, noting that the pharma will “continue to advance the scientific understanding of using siRNA therapy” for cardiovascular diseases and to help people who “still struggle to reach their cholesterol goals.”
Designed to be administered subcutaneously, Leqvio is a siRNA therapy that specifically targets liver cells. Once inside these hepatocytes, Leqvio targets and marks for destruction the mRNA molecule that encodes for the PCSK9, a central player in determining the volume of cholesterol receptors liver cells express. Through this mechanism of action, Leqvio leads to an overall increase in LDL-C receptors, which lowers circulating levels of the cholesterol.
The FDA first approved Leqvio in December 2021, greenlighting its use for lowering LDL-C on top of diet and maximally tolerated statin therapy in patients with ASCVD or heterozygous familial hypercholesterolemia. After an initiation regimen, the therapy is designed to be given only two times a year.
In July 2023, the regulator agreed to an expanded indication of Leqvio, broadening its use to cover patients with elevated LDL-C levels in patients with primary hyperlipidemia who are at risk of heart disease.
Leqvio was originally developed by Alnylam and was licensed by Novartis in January 2020.
