Efficacy of daclatasvir in hepatitis C virus

Abstract

Daclatasvir is a novel NS5A inhibitor of hepatitis C virus (HCV). Daclatasvir combined with peginterferon α-2a and ribavirin in Japanese patients infected with genotype 1b HCV achieved sustained virological response (SVR) in 100% of treatment-naïve patients, due to high rates of favorable IL28B allele and genotype 1b. SVR 24 was achieved by asunaprevir and daclatasvir in 87.4% of intolerant and 80.5% of nonresponder patients. Baseline NS5A-resistant variants were detected and they failed to achieve SVR. Most patients with genotype 1a experienced virological breakthrough by dual oral treatment, and should be treated QUAD or replaced by all oral regimens that are more potent and have fewer side effects. IFN-free regimens including daclatasvir and asunaprevir for genotype 1 null responders should be tailored to subtype, and preexisting NS5A-resistant variants should be evaluated carefully before choosing the drugs. This regimen alone is unlikely to move forward without additional agents.

Keywords::

• asunaprevir
• chronic hepatitis C
• DAA
• daclatasvir
• genotype 1

Financial & competing interests disclosure

This work was supported by a Grant-in-aid from the Japanese Ministry of Health, Welfare and Labor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Daclatasvir is a first-in-class, NS5A replication complex inhibitor with potent pan-genotypic antiviral activity in vitro, and once-daily dosing of 1–100 mg produced a rapid and substantial decrease in hepatitis C virus (HCV)-RNA levels in patients chronically infected with HCV genotype 1.

• Overall response treated by pegIFN and ribavirin plus daclatasvir is higher in Asian studies than in non-Asian studies.

• The dual oral combination treatment with daclatasvir and asunaprevir showed a sustained virological response (SVR) 24 rate from 63.6 to 90.5% in a Phase II study in Japan, but most patients with preexisting NS5A-Y93H polymorphisms did not achieve SVR and emergence of resistance mutations to both the NS5A inhibitor and the protease inhibitor was observed. Preexisting viral variants should be carefully evaluated.

• Dual therapy with daclatasvir plus twice-daily asunaprevir is effective for most genotype 1b patients, but the dual combination therapy was not effective for genotype 1a in Europe and the USA. When genotype 1a patients were treated with QUAD, the SVR 24 rate was reported to be as high as 95%, and the dual oral regimen should be tailored for the subtype.

• Daclatasvir in combination with sofosbuvir provided an SVR 12 rate of 98%. If they have resistant variants to NS5A inhibitors, they should wait treatment until more potent antiviral drugs.

Notes