Novartis' Twice-Yearly siRNA Therapy Leqvio Receives FDA Approval for Expanded Indication as Monotherapy in Hypercholesterolemia

Novartis announced today that the U.S. FDA has approved the expanded indication application for its twice-yearly small interfering RNA (siRNA) therapy Leqvio (inclisiran), allowing it to be used as a monotherapy in combination with diet control and exercise to reduce low-density lipoprotein cholesterol (LDL-C) levels in adults with hypercholesterolemia.According to the press release,The U.S. FDA proactively requested an update to the drug's label based on the positive data from this PCSK9-targeted therapy in lowering LDL-C.

The updated drug label removes the restriction that Leqvio must be used in combination with or on the basis of statins.Other updates also include uniformly revising the term "primary hyperlipidemia" in the label to the more specific "hypercholesterolemia" to emphasize more accurately.LeqvioIn terms of the therapeutic effect on lowering LDL-C.

Cardiovascular disease (CVD) affects hundreds of millions of people worldwide, with related mortality exceeding the combined total of cancer, chronic lung disease, and diabetes. It is estimated that addressing factors causing or exacerbating CVD could prevent approximately 80% of premature deaths caused by CVD. Atherosclerotic cardiovascular disease (ASCVD) accounts for about 85% of all cardiovascular-related deaths. ASCVD is caused by the formation and growth of plaque on the inner walls of arteries, with atherosclerotic plaque primarily composed of LDL-C, which accumulates over time. Persistently elevated levels of LDL-C in the body increase an individual's risk of cardiovascular events such as heart attacks or strokes. Many patients with elevated LDL-C levels also suffer from other conditions like hypertension, obesity, or diabetes, significantly increasing their risk of developing ASCVD and experiencing cardiovascular events.

Leqvio is a“first-in-class”、siRNA Therapy Targeting PCSK9 mRNA,Initially obtained in the United States in December 2021FDA Approval，As an adjunct to diet and statin therapy for the treatment of adult patients with primary hyperlipidemia, including heterozygous familial hypercholesterolemia.（HeFH）Patients, to reduce their LDL-C levels.The role of PCSK9 protein is to inhibitLow-Density LipoproteinRecycling and Reuse of (LDL) Receptors. Therefore,Reducing the level of PCSK9 protein allows more LDL receptors to return to the surface of liver cells, bind with more LDL, and remove them from the bloodstream.The press release pointed out,It is the first siRNA therapy capable of reducing LDL-C.

Last August, NovartisAnnouncementIts V-MONO Phase 3 clinical trial met the primary endpoint. Leqvio, as a monotherapy, significantly reduced LDL-C levels in patients with moderate- to low-risk ASCVD.Analysis shows,Compared with placebo and active control drugs, Leqvio monotherapy demonstrated superiority in reducing LDL-C levels in ASCVD patients., supporting Leqvio as a primary and secondary prevention drug for ASCVD. Primary prevention refers to measures aimed at the general public or individuals to prevent or delay the onset of ASCVD. Secondary prevention involves treating known, clinically significant ASCVD and taking measures to prevent or delay the onset of disease symptoms.

Leqvio must be administered subcutaneously by a healthcare professional, with an initial dose of one injection, followed by another injection three months later, and then one injection every six months.LeqvioThe characteristic of twice-yearly dosing may help improve patient adherence to treatment, a common issue in cholesterol control.Leqvio was initially developed by Alnylam Pharmaceuticals, and Novartis later acquired the global rights for the development, manufacturing, and commercialization of Leqvio.

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[1] Novartis twice-yearly* Leqvio® (inclisiran) receives FDA approval for new indication enabling first-line use. Retrieved July 31, 2025 from https://www.prnewswire.com/news-releases/novartis-twice-yearly-leqvio-inclisiran-receives-fda-approval-for-new-indication-enabling-first-line-use-302519118.html