Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status without Worsening Glycemia

Inclisiran, an investigational PCSK9-specific RNA silencing molecule with potential for a maintenance regimen of twice yearly dosing, significantly lowered LDL-C and PCSK9 in the dose-ranging ORION-1 trial. We report its efficacy and safety by diabetes status, and its impact on glycemia. ORION-1 randomized 501 persons with atherosclerosis (ASCVD) or ASCVD-risk equivalents, and high LDL-C despite maximally tolerated LDL-C lowering therapies, to inclisiran or placebo. Inclisiran significantly lowered LDL-C and PCSK9 similarly in persons with and without diabetes at day 180 (Table). Temporal A1C were similar in the placebo and incisiran arms (Figure). These data suggest that inclisiran is efficacious and does not worsen glycemia in persons with ASCVD or ASCVD-risk equivalents, regardless of their diabetes status, over 180 days. Disclosure L. Leiter: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker9s Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker9s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker9s Bureau; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker9s Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker9s Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker9s Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. Speaker9s Bureau; Self; Sanofi. Advisory Panel; Self; Servier. Speaker9s Bureau; Self; Servier. Research Support; Self; Servier. Advisory Panel; Self; Amgen Inc.. Speaker9s Bureau; Self; Amgen Inc.. Research Support; Self; Amgen Inc., Esperion Therapeutics, Kowa Pharmaceuticals America, Inc., The Medicines Company. Advisory Panel; Self; Akcea Therapeutics, Novartis Pharmaceuticals Corporation. H. Teoh: None. D. Kallend: Employee; Self; The Medicines Company. R. Wright: Consultant; Self; Boehringer Ingelheim GmbH, The Medicines Company, Sanofi-Aventis, Eli Lilly and Company, Regeneron Pharmaceuticals, Inc. U. Landmesser: Advisory Panel; Self; Boehringer Ingelheim GmbH, Medicines Company, Sanofi. Speaker9s Bureau; Self; Amgen Inc. P.L. Wijngaard: Employee; Self; The Medicines Company. Stock/Shareholder; Self; The Medicines Company. J.J. Kastelein: Consultant; Self; The Medicines Company. K.K. Ray: Consultant; Self; Amgen Inc., Sanofi. Research Support; Self; Sanofi. Consultant; Self; The Medicines Company. Research Support; Self; Amgen Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Esperion Therapeutics, Kowa Pharmaceuticals America, Inc.. Research Support; Self; Pfizer Inc.. Consultant; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp..