New analysis of ORION 10 and ORION 11 trials shows high consistency in lowering LDL-C in individual response with investigational inclisiran.- Novartis

Novartis announced results from a post-hoc analysis of pooled data from the Phase III ORION-10 and -11 trials evaluating the individual responses of patients on low-density lipoprotein cholesterol (LDL-C) reduction with inclisiran , a first-in-class investigational treatment for hyperlipidemia in adults. This new analysis of inclisiran showed a highly consistent effect, with a safety and tolerability profile similar to placebo, on a twice-yearly dosing schedule after an initial dose and one 3 months later, across individual patients with atherosclerotic cardiovascular disease (ASCVD) or risk equivalents over 17 months of treatment.Presented at the ESC Congress 2020, the annual meeting of the European Society of Cardiology, the analysis evaluated the efficacy and tolerability of inclisiran on top of a maximally tolerated dose of statins, in two studies of more than 2,300 patients (of which 1,164 were on inclisiran) from the Phase III trials. Results demonstrated a low inter-individual variability, with 99% of inclisiran-treated patients showing a placebo-adjusted greater than 30% reduction of their LDL-C levels with a mean reduction of 54.1% from baseline (observed values). An LDL-C reduction of at least 50% was reached by 88.4% of patients at any time point in the study (observed values). After 17 months, 66.4% of the inclisiran group had a reduction in LDL-C of at least 50% as compared to 2.5% from the placebo group (observed values) . Overall, inclisiran was well-tolerated with a safety profile similar to placebo. All patients were on twice-yearly dosing, following an initial dose and one 3 months later. Inclisiran is currently under review by the FDA and the European Medicines Agency for 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. Data from each of the Phase III studies was recently published online, ahead of print, in The New England Journal of Medicine. A cardiovascular outcomes trial, ORION-4, is ongoing. See- Ray K, Wright R, Kallend D, et al." Two Phase III Trials of Inclisiran in Patients with Elevated LDL Cholesterol". New England Journal of Medicine. 2020;382:1507-1519. See- R. Scott Wright," ORION-10 and ORION-11, Interindividual variability in LDL C reductions with inclisiran". Data presented at the ESC Congress 2020, August 29 - September 1..