In a press release on December 22, 2021, the manufacturer, Novartis, announced that the FDA approved Leqvio (inclisiran), the first and only siRNA therapy to lower LDL-C with two doses a year, after an initial dose and 1 at 3 months. Inclisiran is a double-stranded siRNA, conjugated on the sense strand with triantennary N-Acetylgalactosamine to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for proprotein convertase subtilisin kexin type 9 (PCSK9). This increases LDL-C receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.

Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway.

The FDA approval of Leqvio was based on results from the comprehensive phase III ORION-9, -10 and -11 clinical trials, in which all 3,457 participants with ASCVD or HeFH had elevated LDL-C while receiving a maximally tolerated dose of statin therapy. In the phase III trials at Month 17, Leqvio delivered effective and sustained LDL-C reduction of up to 52% versus placebo and was reported to be well-tolerated with a safety profile demonstrated to be comparable to placebo. The most common adverse effects observed in clinical trials (>3%) included injection-site reaction, arthralgia, urinary tract infection, diarrhea, bronchitis, pain in extremity, and dyspnea.

This novel agent is administered by a healthcare provider. The recommended dosage of Leqvio—in combination with maximally tolerated statin therapy—is 284 mg administered as a single SC injection initially, again at 3 months, and then every 6 months. The medication should be injected SC into the abdomen, upper arm, or thigh. The prescribing information indicates that Leqvio should not be injected in areas of active skin disease or injury, such as sunburns, skin rashes, inflammation, or skin infections. The medication is available as 284 mg/1.5 mL (189 mg/mL) in a single-dose prefilled syringe. Leqvio became available in early January 2022.

In the press release, Novartis CEO Vas Narasimhan stated, "Leqvio is a revolutionary approach to lower LDL-C and creates new possibilities for how healthcare systems can impact cardiovascular disease, a defining public health challenge of our time. We now have the opportunity, working together with partners, to provide this first-ever approved LDL-C—lowering siRNA-based therapy to tackle ASCVD at scale across the United States." 

Additionally, Norman Lepor, MD, a Los Angeles-based cardiologist and a clinical investigator in the phase III clinical program for Leqvio, stated, "ASCVD is a substantial public health burden affecting 30 million Americans. As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target." 

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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