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

Authors

  • A.L. STRAT University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi
  • Cristina Mihaela GHICIUC University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi
  • Catalina Elena LUPUSORU University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi
  • F. MITU University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi

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.

Author Biographies

  • A.L. STRAT, University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi

    Faculty of Medicine
    Department of Morpho-functional Sciences

  • Cristina Mihaela GHICIUC, University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi

    Faculty of Medicine
    Department of Morpho-functional Sciences

  • Catalina Elena LUPUSORU, University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi

    Faculty of Medicine
    Department of Morpho-functional Sciences

  • F. MITU, University of Medicine and Pharmacy “Grigore T. Popa”- Iaşi

    Faculty of Medicine
    Department of Medical Specialties (I)

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Additional Files

Published

2016-06-30

Issue

Vol. 120 No. 2 (2016): The Medical-Surgical Journal

Section

INTERNAL MEDICINE - PEDIATRICS

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