title: A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk.
abstract: Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Tokyo-Eki Center-Building Clinic, Tokyo, Japan. Electronic address: kiyosue-tky@umin.ac.jp.
authors.forename: Arihiro
authors.initials: A
authors.lastname: Kiyosue
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Narimon
authors.initials: N
authors.lastname: Honarpour
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kurtz
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Allen
authors.initials: A
authors.lastname: Xue
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D007564:Japan / Q000453:epidemiology; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; C577155:evolocumab