The Medicines Company announced positive topline results for the ORION-10 Phase 3 clinical study in patients with atherosclerotic cardiovascular disease (ASCVD), successfully completing the pivotal Phase 3 LDL-cholesterol (LDL-C) lowering clinical trials for inclisiran. ORION-10 met all primary and secondary endpoints, and inclisiran demonstrated efficacy, tolerability and safety that were at least as favorable as observed in ORION-11, with no treatment-related liver or renal laboratory abnormalities. Detailed efficacy, tolerability and safety data from ORION-10 will be presented at the American Heart Association (AHA) Scientific Sessions in Philadelphia on Saturday, November 16, 11:06 am EST, during Late Breaking Science I: Outside the Box: New Approaches to CVD Risk Reduction. The company will also present data from the ORION-9 study in patients with Heterozygous Familial Hypercholesterolemia (HeFH) at the AHA congress on Monday, November 18, 9:24am EST, during Late Breaking Science VI: New Frontiers in Lipid Therapy. The ORION program is studying the efficacy and safety of inclisiran in patients with ASCVD and FH, with ORION-9, ORION-10 and ORION-11 comprising the pivotal Phase 3 LDL-C lowering studies. Background on Pivotal Phase 3 LDL-C Lowering Studies: ORION-9 is a pivotal Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of inclisiran sodium 300 mg administered subcutaneously in 482 patients with clinical or genetic evidence of HeFH and elevated LDL-C, despite maximum tolerated dose of LDL-C-lowering therapies (e.g., a statin or ezetimibe). The primary endpoints are percentage change in LDL-C from baseline to day 510 (17 months) and time-adjusted percentage change in LDL-C from baseline between day 90 (three months) and up to day 540 (18 months). Key secondary endpoints include the mean absolute change at Day 510 (17 months), the average absolute reduction from Day 90 (three months) up to Day 540 (18 months), and changes in other lipids and lipoproteins. The international study was conducted at 54 sites in eight countries. Each study participant received inclisiran sodium 300 mg administered as a subcutaneous injection initially, again at three months and then every six months thereafter. The majority of study participants are taking inclisiran or placebo in addition to existing lipid-lowering therapy with a maximally tolerated statin (with or without ezetimibe); ORION-10 is a pivotal Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of inclisiran sodium 300 mg administered subcutaneously in 1,561 participants with ASCVD and elevated LDL-C, despite maximum tolerated dose of LDL-C-lowering therapies (e.g., a statin or ezetimibe). The primary endpoints are percentage change in LDL-C from baseline to day 510 (17 months) and time-adjusted percentage change in LDL-C from baseline after day 90 (three months) and up to day 540 (18 months). The majority of study participants are taking inclisiran or placebo in addition to existing lipid-lowering therapy with a maximally tolerated statin (with or without ezetimibe). Key secondary endpoints include the mean absolute change at Day 510 (17 months), the average absolute reduction from Day 90 (three months) up to Day 540 (18 months), and changes in other lipids and lipoproteins. The study was conducted at 145 sites in the United States. Each study participant received inclisiran sodium 300 mg administered as a subcutaneous injection initially, again at three months and then every six months thereafter. The majority of study participants are taking inclisiran or placebo in addition to existing lipid-lowering therapy with a maximally tolerated statin (with or without ezetimibe); ORION-11 is a pivotal Phase 3, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety, and tolerability of inclisiran sodium 300 mg administered subcutaneously in 1,617 patients with ASCVD or ASCVD-risk equivalents and elevated LDL-C despite maximum tolerated dose of statin therapy (with or without ezetimibe). In ORION-11, twice-yearly dosing with inclisiran sodium 300 mg met all primary and secondary efficacy endpoints, was well-tolerated and demonstrated an excellent safety profile. Detailed study results were presented during a late-breaking science session at the European Society of Cardiology’s ESC Congress 2019 in Paris on September 2.