Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection.
OBJECTIVE
To review the pharmacology, efficacy, and safety of daclatasvir in the treatment of patients with chronic hepatitis C virus (HCV) infection.


METHODS
A literature search through EMBASE and PubMed was conducted (January 1966 to August 2015) using the terms BMS-790052, daclatasvir, and hepatitis C. References from retrieved articles were reviewed for any additional material. Additionally, the new drug application and prescribing information were retrieved.


METHODS
The literature search was limited to human studies published in English. Phase 1, 2, and 3 studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daclatasvir for HCV were identified.


RESULTS
Daclatasvir, a nonstructural 5A protein inhibitor, combined with sofosbuvir, is indicated for adult patients with chronic HCV genotype 3 regardless of treatment or cirrhosis status. The phase III ALLY-3 trial (n = 152) demonstrated that daclatasvir taken once daily with sofosbuvir for 12 weeks was effective at achieving sustained virological response (SVR) rates in treatment-naïve (97%) and treatment-experienced (94%) patients without cirrhosis. Patients with cirrhosis had significantly lower SVR rates (58 and 69%, respectively). The most common adverse drug events associated with daclatasvir and sofosbuvir in ALLY-3 were headache (20%), fatigue (19%), and nausea (12%).


CONCLUSIONS
Daclatasvir, when combined with sofosbuvir, is an effective agent to treat HCV genotype 3, with SVR rates above 90% for patients without cirrhosis who are treatment naïve or experienced. SVR rates for treatment-naïve or -experienced patients with cirrhosis are not as robust (58%-69%).
University of the Sciences, Philadelphia, PA, USA.
Michael A
MA
Smith
University of Michigan, MI, USA.
Randolph E
RE
Regal
University of Michigan, MI, USA rimam@med.umich.edu.
Rima A
RA
Mohammad
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005838:Genotype; D006261:Headache / Q000139:chemically induced; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy; D009325:Nausea / Q000139:chemically induced; D011759:Pyrrolidines; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D000069474:Sofosbuvir; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir
BMS-790052; NS5A inhibitor; daclatasvir; hepatitis C