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 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.