Inclisiran

Inclisiran is a lipid-lowering therapy that uses RNA interference to reduce low-density lipoprotein cholesterol (LDL-C). It is a small interfering RNA (siRNA) molecule designed to silence the mRNA for proprotein convertase subtilisin/kexin type 9 (PCSK9), thereby lowering PCSK9 protein levels and increasing LDL receptor activity in the liver. The siRNA is conjugated to a hepatocyte-targeting ligand (GalNAc) to enhance liver uptake and achieve sustained LDL-C reduction after a few injections. It is marketed under the brand Leqvio in many regions and was developed through collaboration involving Alnylam and Novartis.

Regimen and administration

Inclisiran is given as a subcutaneous injection. The approved dosing schedule is 284 mg on day 0, then a second dose at day 90 (about 3 months), followed by injections every 6 months thereafter. It is intended to be used in addition to diet and maximally tolerated statin therapy in adults.

Indications

In adults, inclisiran is indicated to reduce LDL-C in combination with diet and statin therapy for the treatment of heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. It is used to achieve additional LDL-C lowering beyond statins alone.

Efficacy and safety

Clinical trials have demonstrated approximately a 50% reduction in LDL-C from baseline with sustained effects over time. The safety profile is generally favorable; the most common adverse events are injection-site reactions, along with occasional flu-like symptoms and nasopharyngitis. As with other therapies, liver function and lipid response should be monitored as clinically indicated.

Regulatory status

Inclisiran was approved in the European Union in 2020 and subsequently in the United States in 2021.