Twice-yearly dosing with inclisiran sodium resulted in significant lowering of low-density lipoprotein (LDL) cholesterol, according to results from the ORION-9 study. Findings were presented at the American Heart Association Scientific Sessions in Philadelphia, PA. 

Inclisiran is a chemically synthesized small interfering RNA (siRNA) that targets proprotein convertase subtilisin-kexin type 9 (PCSK9) messenger RNA. The subcutaneous (SC) injectable is being investigated for its ability to lower LDL-C through twice-a-year dosing.

In the ORION-9 study (N=482), patients with clinical or genetic evidence of heterozygous familial hypercholesterolemia (HeFH) and elevated LDL-C, despite maximally tolerated doses of LDL-C-lowering therapies (eg, a statin or ezetimibe) were randomized to receive either inclisiran 300mg SC or placebo on Day 1, Day 90, and then every 6 months up to Day 540. The primary end point of the study was the percentage change in LDL-C from baseline to Day 510 and the time-adjusted percentage change in LDL-C from baseline after Day 90 to Day 540.

Findings from the study showed that treatment with inclisiran resulted in placebo-adjusted LDL-C reductions of 50% (71mg/dL, P<.0001) at Day 510 and time-adjusted LDL-C reductions of 45% (63mg/dL, P <.0001) from Days 90 through 540. Commenting on the results from the ORION-9 study principal investigator Frederick J. Raal, MBBCh, PhD, Professor and Head of the Division of Endocrinology and Metabolism, University of the Witwatersrand, Johannesburg, South Africa, said: “The results from ORION-9 support inclisiran’s profile as an important and promising potential therapy option in patients with this inherited form of hypercholesterolemia.”

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With regard to safety, the overall adverse events profile was found to be similar between the 2 arms; no treatment-related hepatic or renal abnormalities were observed. Injection-site reactions, though mild and transient, were reported more frequently with inclisiran compared with placebo (13.7% vs 0.4%). 

The Company plans to submit a New Drug Application with the Food and Drug Administration in the fourth quarter of 2019.

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