title: Efficacy and safety profile of evolocumab (AMG145), an injectable inhibitor of the proprotein convertase subtilisin/kexin type 9: the available clinical evidence.
abstract: BACKGROUND
  Despite the proven efficacy of statins, they are often reported to be inadequate to achieve low-density lipoprotein cholesterol (LDL-C) goals (especially in high-risk patients). Moreover, a large number of subjects cannot tolerate statins or full doses of these drugs. Thus, there is a need for additional effective LDL-C reducing agents.
  
  
  METHODS
  Evolocumab (AMG145) is a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation. Phase I and II trials revealed that its subcutaneous injection, either alone or in combination with statins, is able to reduce LDL-C from 40 to 80%, apolipoprotein B100 from 30 to 59% and lipoprotein(a) from 18 to 36% in a dose-dependent manner. The incidence of side effects seems to be low and mainly limited to nasopharyngitis, injection site pain, arthralgia and back pain.
  
  
  CONCLUSIONS
  Evolocumab is an innovative powerful lipid-lowering drug, additive to statins and with an apparently large therapeutic range associated to a low rate of mild adverse events. If available data will be confirmed in long-term trials with strong outcomes, Evolocumab will provide an essential tool to treat high-risk patients who need to reach ambitious LDL-C target.
authors.affiliation: S. Orsola-Malpighi University Hospital, Medical and Surgical Sciences Department, Internal Medicine Unit , Pad. 2, Via Albertoni 15, 40138 Bologna , Italy +39 3498558017 ; +39 0516826125 ; afgcicero@cardionet.it , arrigo.cicero@unibo.it.
authors.forename: Arrigo F G
authors.initials: AF
authors.lastname: Cicero
authors.forename: Elisa
authors.initials: E
authors.lastname: Tartagni
authors.forename: Sibel
authors.initials: S
authors.lastname: Ertek
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D000960:Hypolipidemic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab
keywords: AMG145; hypercholesterolemia; lipid-lowering drugs; proprotein convertase subtilisin/kexin type 9