NS5A inhibitor, daclatasvir, for the treatment of chronic hepatitis C virus infection.
BACKGROUND
Chronic Hepatitis C virus (HCV) infection is a major pandemic. The current standard of care includes peginterferon and ribavirin plus one of two protease inhibitors, boceprevir and telaprevir, for Genotype 1 patients and peginterferon and ribavirin for all other genotypes. The treatment landscape is rapidly evolving as a number of direct-acting antivirals (DAA) are being developed in clinical trials.


METHODS
Daclatasvir, formerly labeled BMS-790052, is a first-in-class HCV NS5A inhibitor that has been demonstrated in Phase I and II trials to have a very potent antiviral effect across all genotypes and to have a potent clinical efficacy in both treatment naive and experienced cohorts. This review covers the whole spectrum of development of daclatasvir from Phase I to III programs.


CONCLUSIONS
While daclatasvir has pangenotypic activity, it has a lower barrier to resistance in Genotype 1a but has been found to be very effective in Genotype 1b patients. However, Genotype 1a patients can be successfully treated with the addition of one or more DAAs alone or in combination with peginterferon and ribavirin. The future for daclatasvir and other DAAs is very encouraging in that all-oral therapies are likely to be effective and well-tolerated.
University of Pennsylvania, Department of Gastroenterology Research , Philadelphia, PA 19104 , USA.
D Alan
DA
Herbst
K Rajender
KR
Reddy
D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002219:Carbamates; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D024882:Drug Resistance, Viral / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015394:Molecular Structure; D011759:Pyrrolidines; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir