title: Biologics for the treatment of dyslipidemias: a look beyond conventional therapy.
abstract: OBJECTIVE
  To evaluate the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) in the management of dyslipidemias.
  
  
  METHODS
  MEDLINE/PubMed, NHS Evidence, TRIP database and EMBASE searches were conducted using the terms proprotein convertase subtilisin/kexin type 9, PCSK9, and monoclonal antibody. No date limits were utilized; search results were current to September 2013.
  
  
  METHODS
  Articles were limited to phase 2 or 3 clinical trials of monoclonal antibodies to PCSK9 assessing surrogate markers of clinical end points.
  
  
  RESULTS
  AMG145 and REGN727/SAR236553 are human monoclonal antibodies to PCSK9, a serine protease responsible for low-density lipoprotein cholesterol (LDL-C) regulation. PCSK9 binds to LDL receptors targeting them for intracellular degradation. AMG145 and REGN727/SAR236553 blocks the interaction between PCSK9 and the LDL receptor, increasing LDL receptor availability and allowing the removal of LDL-C from the circulation. These therapies have been evaluated as monotherapy and in combination with statins and ezetimibe in phase 2 trials and have demonstrated significant and dose-related reductions in LDL-C. LDL-C reductions were as high as 72% with REGN727/SAR236553 and 66% with AMG145. These agents were generally well tolerated; nasopharyngitis and injection site reactions were the most common reactions with both agents. Gastrointestinal disturbances and infections were also common with REGN727/SAR236553.
  
  
  CONCLUSIONS
  These agents may eventually play a role as add-on therapy in those with dyslipidemias because of their significant effect on LDL-C. Further explorations in large phase 3 clinical trials are warranted to evaluate the effect of these therapies on cardiovascular clinical outcomes and long-term safety.
authors.affiliation: University of Maryland School of Pharmacy, Baltimore, MD, USA.
authors.forename: Connie H
authors.initials: CH
authors.lastname: Yoon
authors.forename: Kristin
authors.initials: K
authors.lastname: Watson
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000187:drug effects; D050171:Dyslipidemias / Q000188:drug therapy*; D000069438:Ezetimibe; D006801:Humans; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D001384:Azetidines; D001688:Biological Products; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe
keywords: AMG145; PCSK9; REGN727/SAR236553; dyslipidemia; monoclonal antibody; proprotein convertase subtilisin/kexin type 9