NEW CLASS OF DRUGS: THERAPEUTIC RNAi INHIBITION OF PCSK9 AS A SPECIFIC LDL-C LOWERING THERAPY

Hyperlipidemia is a well-known risk factor for coronary heart disease, the leading cause of death for both men and women. Current lipidlowering 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-inclass therapeutic RNA interference (RNAi) inhibitor of proprotein convertase subti lisin/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 r 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.