Treatment with twice-yearly inclisiran consistently reduced low-density lipoprotein cholesterol (LDL-C) levels over a period of 17 months, according to a post-hoc analysis of pooled data from the two phase 3 trials presented at the European Society of Cardiology (ESC) Congress 2020.
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.
The post-hoc analysis included 2 randomized, double-blind, placebo-controlled phase 3 studies (ORION-10 and -11) that evaluated the efficacy and safety of inclisiran sodium in more than 2300 adult patients. The ORION-10 study included patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C, despite a maximum tolerated dose of LDL-C-lowering therapies (eg, statin or ezetimibe). The ORION-11 study included patients with ASCVD or ASCVD-risk equivalents and elevated LDL-C despite a maximum tolerated dose of statin therapy (with or without ezetimibe). All patients were randomized to receive either inclisiran 300mg SC or placebo on day 1, again at 3 months, then every 6 months thereafter.
Findings from the analysis showed that 99% of patients treated with inclisiran had a placebo-adjusted reduction in LDL-C of ≥30% with a mean reduction of 54.1% from baseline (observed values). Additionally, 88.4% of inclisiran-treated patients had at least a 50% reduction in LDL-C levels at any time point during the study (observed values). After 17 months, an LDL-C reduction of at least 50% was achieved by 66.4% of the inclisiran group compared with 2.5% for the placebo group (observed values).
“This analysis confirms that as a small interfering RNA, inclisiran provides a remarkably consistent treatment profile,” said ORION-11 principal investigator Kausik Ray, MD, Professor of Public Health, Consultant Cardiologist, Imperial College London. “Nearly all patients from these trials achieved clinically meaningful reductions of their LDL-C levels over the 17 month period, and inclisiran had a safety and tolerability profile similar to placebo.”
The Food and Drug Administration (FDA) is currently reviewing the New Drug Application (NDA) for inclisiran in the treatment of primary hyperlipidemia (including heterozygous familial hypercholesterolemia) in adults who have elevated LDL-C while being on a maximally tolerated dose of statin therapy.
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Novartis new analysis shows high consistency in lowering LDL-C in individual response with investigational inclisiran. https://www.prnewswire.com/news-releases/novartis-new-analysis-shows-high-consistency-in-lowering-ldl-c-in-individual-response-with-investigational-inclisiran-301120583.html. Accessed August 31, 2020.