title: Systematic review of published Phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia.
abstract: Two anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, have been approved for the treatment of hypercholesterolaemia in certain patients. We reviewed data from Phase 3 studies to evaluate the efficacy and safety of these antibodies.
  
  
  
  We systematically reviewed Phase 3 English-language studies in patients with hypercholesterolaemia, published between 1 January 2005 and 20 October 2015. Congress proceedings from 16 November 2012 to 16 November 2015 were also reviewed.
  
  
  
  We identified 12 studies of alirocumab and nine of evolocumab, including over 10 000 patients overall. Most studies enrolled patients with hypercholesterolaemia and used anti-PCSK9 antibodies with statins. The ODYSSEY FH I, FH II and HIGH FH alirocumab studies and the RUTHERFORD-2 evolocumab study exclusively recruited patients with heterozygous familial hypercholesterolaemia. Two evolocumab studies focused mainly on homozygous familial hypercholesterolaemia (HoFH): TESLA Part B and TAUSSIG (a TESLA sub-study); only those data for HoFH are reported here. All comparator studies demonstrated a reduction in LDL cholesterol (LDL-C) with the anti-PCSK9 antibodies. No head-to-head studies were conducted between alirocumab and evolocumab. Up to 87% of patients receiving alirocumab and up to 98% receiving evolocumab reached LDL-C goals. Both antibodies were effective and well tolerated across a broad population of patients and in specific subgroups, such as those with type 2 diabetes.
  
  
  
  Using anti-PCSK9 antibodies as add-on therapy to other lipid-lowering treatments or as monotherapy for patients unable to tolerate statins may help patients with high cardiovascular risk to achieve their LDL-C goals.
authors.affiliation: Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP), University of Cologne, Cologne, Germany.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gouni-Berthold
authors.affiliation: Department of Internal Medicine, Centres Hospitaliers Jolimont, Haine Saint-Paul, Belgium.
authors.forename: Olivier S
authors.initials: OS
authors.lastname: Descamps
authors.affiliation: Amgen GmbH, Munich, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Fraass
authors.affiliation: Oxford PharmaGenesis Ltd, Oxford, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hartfield
authors.affiliation: Oxford PharmaGenesis Ltd, Oxford, UK.
authors.forename: Kim
authors.identifier: 0000-0001-6556-2002
authors.initials: K
authors.lastname: Allcott
authors.affiliation: Amgen (Europe) GmbH, Zug, Switzerland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dent
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria.|Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Germany.|Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim and Augsburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000378:metabolism; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab; C571059:alirocumab
keywords: LDL cholesterol; PCSK9; alirocumab; evolocumab; hypercholesterolemia; lipoproteins