What is Leqvio (inclisiran)?

From the Guidelines

Leqvio (inclisiran) is recommended as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-C, due to its ability to lower LDL-C by a mean of 50.7% at day 510, as demonstrated in a pooled patient-level analysis of 3,660 patients in phase 3 trials 1. The medication works by selectively and catalytically silencing the translation of PCSK9 messenger ribonucleic acid, thereby up-regulating LDL receptor density on hepatocytes and inhibiting hepatic translation of the PCSK9 protein. Some key points to consider when prescribing Leqvio include:

• The recommended dosage is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months thereafter.
• Common side effects include injection site reactions, which were more frequent with Leqvio than with placebo (5.0% vs 0.7%) but were predominantly mild, and none was severe or persistent 1.
• Leqvio is particularly beneficial for patients with ASCVD or HeFH who haven't achieved target LDL levels with statins alone, and its twice-yearly administration by subcutaneous injection offers a convenient alternative to other cholesterol medications that require more frequent dosing.
• It is essential to note that the effect of Leqvio on cardiovascular morbidity and mortality has not been determined, but two cardiovascular outcomes trials, ORION-4 and VICTORION-2P, are currently in progress to assess its impact on major adverse cardiovascular events 1.

From the FDA Drug Label

LEQVIO is a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA indicated as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce low-density lipoprotein cholesterol (LDL-C). LEQVIO contains inclisiran sodium, a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA.

LEQVIO (inclisiran) is a medication used to treat primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), by reducing low-density lipoprotein cholesterol (LDL-C) in adults, as an adjunct to diet and statin therapy 2.

• The medication works by targeting proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA using small interfering RNA (siRNA) technology.
• LEQVIO is administered via subcutaneous injection and is available in a prefilled syringe containing 284 mg of inclisiran 3.

From the Research

Leqvio Overview

• Leqvio, also known as inclisiran, is a first-in-class, subcutaneously administered, small interfering RNA (siRNA) that prevents hepatic synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) 4.
• It is indicated in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet, and is intended for use in patients unable to reach LDL-C goals on maximally tolerated statin therapy, with or without other lipid-lowering therapies (LLTs) 4, 5.

Mechanism of Action and Efficacy

• Inclisiran decreases circulating low-density lipoprotein cholesterol (LDL-C) by preventing the hepatic synthesis of PCSK9 4.
• Clinical trials have shown that twice-yearly injections of inclisiran can approximately halve LDL-C levels in patients with hypercholesterolemia, irrespective of whether or not their existing treatment included a statin 4.
• The efficacy of inclisiran is maintained in the longer term, and it is well tolerated, with a safety and tolerability profile similar to placebo, although mild to moderate, transient injection-site adverse reactions are more frequent with inclisiran 4.

Comparison with Other Lipid-Lowering Therapies

• Other lipid-lowering therapies, such as evolocumab and alirocumab, have also been shown to be effective in reducing LDL-C levels and cardiovascular risk 6, 7, 8.
• However, the evidence base for the clinical endpoint effects of these therapies is stronger for evolocumab and alirocumab compared to inclisiran, and it is unclear whether inclisiran might be effectively used as a replacement therapy 8.

Safety and Tolerability

• The safety and tolerability profile of inclisiran is similar to placebo, although mild to moderate, transient injection-site adverse reactions are more frequent with inclisiran 4.
• There is limited evidence on the potential safety issues of inclisiran, and careful consideration of alternative lipid-lowering treatments should be taken before prescribing inclisiran 8.