title: NEW CLASS OF DRUGS: THERAPEUTIC RNAi INHIBITION OF PCSK9 AS A SPECIFIC LDL-C LOWERING THERAPY.
abstract: Hyperlipidemia is a well-known risk factor for coronary heart disease, the leading cause of death for both men and women. Current lipid-lowering treatment is not always efficient, therefore new pharmacological interventions that reduce LDL cholesterol (LDL-C) have been developed. This paper presents new class of specific LDL lipid-lowering drugs under investigation in phase II or III clinical trials. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key enzyme in cholesterol homeostasis, improve the liver's ability to clear LDL from the plasma, reducing LDL-C levels. Currently, three monoclonal antibodies PCSK9 inhibitors (alirocumab, evolocumab and bococizumab) are evaluated in clinical outcome trials. ALN-PCSsc, the new first-in- class therapeutic RNA interference (RNAi) inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) is also the first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver. The development leadership of ALN-PCSsc has now transferred from Alnylam Pharmaceuticals to The Medicines Company, who has initiated the ORION-1 Phase II study at the beginning of 2016. ALN-PCSsc has significant potential given its highly competitive profile as compared with monoclonal antibodies anti-PCSK9 MAbs, a recently approved class of LDL-C lowering drugs.
authors.forename: A L
authors.initials: AL
authors.lastname: Strat
authors.forename: Cristina Mihaela
authors.initials: CM
authors.lastname: Ghiciuc
authors.forename: Cătălina Elena
authors.initials: CE
authors.lastname: Lupuşoru
authors.forename: F
authors.initials: F
authors.lastname: Mitu
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000187:drug effects*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003324:Coronary Artery Disease / Q000517:prevention & control*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000187:drug effects*; D034622:RNA Interference / Q000187:drug effects*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; C000598888:bococizumab; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C577155:evolocumab; C571059:alirocumab