title: Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab.
abstract: OBJECTIVE
  The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase III trial.
  
  
  BACKGROUND
  Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials.
  
  
  METHODS
  Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; or oral placebo and evolocumab 420 mg monthly.
  
  
  RESULTS
  A total of 614 patients were randomized and administered doses. Evolocumab treatment reduced LDL-C from baseline, on average, by 55% to 57% more than placebo and 38% to 40% more than ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment also favorably altered other lipoprotein levels. Treatment-emergent adverse events (AEs), muscle-related AEs, and laboratory abnormalities were comparable across treatment groups.
  
  
  CONCLUSIONS
  In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; NCT01763827).
authors.affiliation: Jacksonville Center for Clinical Research, Jacksonville, Florida. Electronic address: mkoren@encoredocs.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Koren
authors.affiliation: Center for Clinical and Basic Research, Ballerup, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Lundqvist
authors.affiliation: Bethesda Health Research Center, Bethesda, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Bolognese
authors.affiliation: Orange County Research Center, Tustin, California.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Neutel
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Monsalvo
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Jae B
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Rob
authors.initials: R
authors.lastname: Scott
authors.affiliation: Amgen Inc., Thousand Oaks, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Wasserman
authors.affiliation: L-MARC Research Center, Louisville, Kentucky.
authors.forename: Harold
authors.initials: H
authors.lastname: Bays
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000097:blood; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab
keywords: PCSK9 inhibition; dyslipidemia; evolocumab; monotherapy