General Information

Leqvio (inclisiran) is a small interfering RNA (siRNA).

Leqvio is specifically indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low density lipoprotein cholesterol (LDL-C). The FDA subsequently expanded the label to enable earlier use in patients with elevated LDL-C who have an increased risk of heart disease, as an adjunct to diet and statin therapy.

Leqvio is supplied as an injection for subcutaneous administration. 

The recommended dosage of Leqvio, in combination with maximally tolerated statin therapy, is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months. If a planned dose is missed by less than 3 months, administer Leqvio and maintain dosing according to the patient’s original schedule. If a planned dose is missed by more than 3 months, restart with a new dosing schedule - administer Leqvio initially, again at 3 months, and then every 6 months. Assess LDL-C when clinically indicated. The LDL-lowering effect of Leqvio may be measured as early as 30 days after initiation and anytime thereafter without regard to timing of the dose.

Mechanism of Action

Leqvio (inclisiran) is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-Acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for 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.

Side Effects

• injection site reaction
• arthralgia
• urinary tract infection
• diarrhea
• bronchitis
• pain in extremity
• dyspnea

Clinical Trial Results

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% vs. placebo.