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.”
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.
For more information visit themedicinescompany.com.