Inclisiran

[5][7][6][9] It is a small interfering RNA (siRNA) that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein PCSK9.

[7] 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).

[10] Studies of PCSK9 genetics supported the conclusion that decreases in circulating LDL cholesterol accomplished in this way would result in "diminished cardiovascular risk... with no apparent negative health consequences", and long term administration of antibodies with short in vivo half-lives, 1-2 times a month, reduced circulating PCSK9 and LDL cholesterol levels, with the result of a "lower incidence of cardiovascular events than placebo".

[10] Together, these results contributed to the validation of PCSK9-targeting siRNAs for development as a new therapeutic for use in LDL cholesterol–lowering therapy; specifically, small interfering RNA (siRNA) molecules of appropriate sequence and structure[clarification needed] were sought and discovered as a means of decreasing PCSK9 levels, and the development of a clinical candidate ensued thereafter.

[6][9] Enrolled participants were taking maximally tolerated statin therapy but required additional LDL-C lowering based on their risk for cardiovascular events.

[6] In all three studies, the main effectiveness outcome measure was the percent change in LDL-C from the beginning of the trial to day 510 (month 17).