title: Safety and efficacy of alirocumab 150 mg every 2 weeks, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody: A Phase II pooled analysis.
abstract: BACKGROUND
  Alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is in Phase III development for the treatment of hypercholesterolemia. In Phase II studies, 150 mg every 2 weeks (Q2W) was the highest Q2W dose studied, and it is currently the highest Q2W dose under development. To better assess the safety and efficacy of this dose, data across three Phase II studies were pooled.
  
  
  METHODS
  We analyzed data from three double-blind, randomized, placebo-controlled Phase II studies of 8 or 12 weeks' duration. In the current analysis, 77 patients were randomized to the control group and 108 were randomized to alirocumab 150 mg Q2W administered via a single 1 mL subcutaneous injection.
  
  
  RESULTS
  Adverse events (AEs) occurred in 58.3% of alirocumab patients compared with 54.5% of placebo-controlled patients. The most common AE was mild, transient injection-site reactions. No signal for muscle symptoms such as myalgia and no cases of neurocognitive effects were reported or observed. One alirocumab patient, also receiving atorvastatin 80 mg/day, had an increase in aspartate transaminase 3 to 5 times the upper limit of normal. Alirocumab 150 mg Q2W reduced low-density lipoprotein cholesterol (LDL-C) from baseline by 68.4% compared with 10.5% for the control group. More than 90% of patients achieved an LDL-C target of < 70 mg/dL with alirocumab versus 8% with control. Marked reductions in other atherogenic lipids and modest increases in high-density lipoprotein cholesterol were also observed.
  
  
  CONCLUSIONS
  At the highest Q2W dose under development (150 mg), alirocumab appears well tolerated and produces robust LDL-C reductions. These data suggest that alirocumab 150 mg Q2W is an appropriate dose for further evaluation in Phase III trials.
authors.affiliation: Jacksonville Center for Clinical Research , Jacksonville, FL , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Koren
authors.forename: Eli M
authors.initials: EM
authors.lastname: Roth
authors.forename: James M
authors.initials: JM
authors.lastname: McKenney
authors.forename: Daniel
authors.initials: D
authors.lastname: Gipe
authors.forename: Corinne
authors.initials: C
authors.lastname: Hanotin
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Ferrand
authors.forename: Richard
authors.initials: R
authors.lastname: Wu
authors.forename: Robert
authors.initials: R
authors.lastname: Dufour
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000097:blood; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C571059:alirocumab
keywords: Alirocumab; hypercholesterolemia; low-density lipoprotein cholesterol; proprotein convertase subtilisin/kexin type 9