The Medicines Company Presents Clinical Data Analyses for Inclisiran at 87th European Atherosclerosis Society Congress - Seite 2

ORION-1 and ORION-7

The aim of the combined analysis of data from ORION-1 and ORION-7 was to determine whether dose adjustment of inclisiran was necessary for patients with impaired renal function. Therefore, the objectives were to evaluate the pharmacokinetics and pharmacodynamics in patients across a range of renal function levels and to assess the relationship between estimated glomerular filtration rate (eGFR, a measure of renal function) and adverse events.

The analysis demonstrated that patients who received inclisiran sodium 300 mg achieved consistent reductions in LDL-C and proprotein convertase subtilisin-kexin type 9 (PCSK9) regardless of renal status at study entry. Among all patients in the analysis, treatment-emergent adverse event rates were not influenced by renal impairment and were not different from placebo. There was no relationship between inclisiran administration and eGFR levels, including no exacerbation of renal impairment. No dose adjustment of inclisiran was required for patients with renal impairment (mild, moderate or severe).

ORION-1 (N=501) is a Phase 2, placebo-controlled, double-blind, randomized trial to evaluate the efficacy, safety, and tolerability of inclisiran in participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies. The trial compares the effect of different doses of inclisiran and evaluates the potential for an infrequent dosing regimen. The primary endpoint of the trial is the percentage change in LDL-C from baseline to day 180. A sub-group analysis was performed to evaluate long-term pharmacodynamics and safety of a single-dose (N=60) or two doses (N=59) of inclisiran sodium 300 mg in subjects with normal renal function or with mild or moderate renal impairment.

ORION-7 (N=31) is a Phase 1, single-dose, open-label trial to evaluate the effects of a single dose of inclisiran sodium 300 mg in participants with mild, moderate and severe renal impairment compared to participants with normal renal function. The primary endpoint is to determine the pharmacokinetic and pharmacodynamic parameters, as well as safety, of inclisiran in subjects with normal and impaired renal function at 48 hours post-dose. Secondary endpoints include changes from baseline in lipids and lipoproteins, as well as PCSK9, to day 60.