title: Bococizumab for the treatment of hypercholesterolaemia.
abstract: Low-density lipoprotein cholesterol (LDL-C) remains a well-established risk factor for cardiovascular disease (CVD). LDL-C levels are considered primary targets of therapy. A new series of systemic biomolecules, the monoclonal antibodies (mAbs) of proprotein convertase subtilisin/kexin type 9 (PCSK9), have a higher activity in reducing LDL-C. Areas covered: The authors critically review the current evidence on the efficacy and safety of bococizumab, a humanized mAb against PCSK9, which was surprisingly discontinued in November 2016. The pharmacokinetic profile and the biological features of bococizumab vs others mAbs are also discussed. As of now, in adjunct to diet, alirocumab and evolocumab are the only approved PCSK9 mAbs for the treatment of adult patients with severe clinical atherosclerotic CVD already at maximally-tolerated statin therapy and require additional LDL-C lowering. Expert opinion: Although discontinued, data from a phase 2b trial show the effectiveness of bococizumab in lowering LDL-C in a similar way to the two available PCSK9 antagonists. However, some peculiar biological characteristics of bococizumab may explain the attenuation of LDL-C lowering over time, as well as a higher rate of immunogenicity and of injection-site reactions.
authors.affiliation: a Department of Pharmaceutical and Pharmacological Sciences , Università di Padova , Padua , Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferri
authors.affiliation: b Dipartimento di Scienze Farmacologiche e Biomolecolari , Università degli Studi di Milano , Milan , Italy.|c Multimedica IRCCS , Milano , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Corsini
authors.affiliation: d Centro Dislipidemie , A.S.S.T. Grande Ospedale Metropolitano Niguarda , Milan , Italy.
authors.forename: Cesare R
authors.initials: CR
authors.lastname: Sirtori
authors.affiliation: b Dipartimento di Scienze Farmacologiche e Biomolecolari , Università degli Studi di Milano , Milan , Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D000091362:PCSK9 Inhibitors; D012307:Risk Factors; D016896:Treatment Outcome; D000071449:Proprotein Convertase 9
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C000598888:bococizumab; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Bocucizumab; LDL-C; PCSK9; familial hypercholesterolaemias; humanized monoclonal antibody