Inclisiran, sold under the brand name Leqvio, is a medication for the treatment of people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk-equivalents, and heterozygous familial hypercholesterolemia (HeFH). It is a small interfering RNA (siRNA) that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein PCSK9.Inclisiran was approved for use in the European Union in December 2020. In August 2021, it received NICE approval for use by the National Health Service in the UK. In December 2021, it was approved for medical use in the United States. Medical uses
In the European Union, inclisiran is indicated in adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in people unable to reach LDL-C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid-lowering therapies in people who are statin-intolerant, or for whom a statin is contraindicated.In the United States, it is 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). Discovery and mechanism of action
Inclisiran is a small interfering RNA that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein termed proprotein convertase subtilisin/kexin type 9 (PCSK9).
At day 510, the inclisiran group had an average LDL-C decrease of 51% whereas the placebo group had an average LDL-C increase of 1%. Study 2 enrolled 1,414 adults with ASCVD. At day 510, the inclisiran group had an average LDL-C decrease of 46% whereas the placebo group had an average LDL-C increase of 4%. Study 3 enrolled 482 adults with HeFH. At day 510, the inclisiran group had an average LDL-C decrease of 40% whereas the placebo group had an average LDL-C increase of 8%.The effect of inclisiran on cardiovascular morbidity (suffering from a disease) and mortality (death) has not been determined. References
Further reading
Ray KK, Landmesser U, Leiter LA,  et al. (April 2017). "Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol" (PDF). N. Engl. J. Med. 376 (15): 1430–1440. doi:10.1056/NEJMoa1615758. hdl:10044/1/45416. PMID 28306389. S2CID 205101529. Ray KK, Wright RS, Kallend D,  et al. (March 2020). "Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol". N. Engl. J. Med. 382 (16): 1507–1519. doi:10.1056/NEJMoa1912387. PMID 32187462. External links
"Inclisiran". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03399370 for "Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol (ORION-10)" at ClinicalTrials.gov
Clinical trial number NCT03400800 for "Inclisiran for Subjects With ACSVD or ACSVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol (ORION-11)" at ClinicalTrials.gov
Clinical trial number NCT03397121 for "Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) (ORION-9)" at ClinicalTrials.gov