Asunaprevir (BMS-650032) for the treatment of hepatitis C virus

Abstract

Asunaprevir, a second-generation NS3 protease inhibitor of hepatitis C virus (HCV), exhibits strong antiviral activity against HCV genotypes 1 and 4, but relatively weak activity against genotypes 2 and 3. For chronic HCV infection, asunaprevir with daclatasvir as an interferon-free dual treatment achieves a sustained virologic response of nearly 90% in genotype 1b, and a triple regimen with beclabuvir achieves an sustained virologic response >90%. Asunaprevir and daclatasvir dual treatment can be safely and effectively administered to liver transplant recipients with recurrent HCV. The major drawback of asunaprevir is its low threshold to resistance, which can be overcome by combining it with other direct-acting antivirals. Further studies of asunaprevir in combination with other direct-acting antivirals for the treatment of patients with HCV genotypes 1 or 4 and renal impairment or end-stage renal disease under hemodialysis, HIV-coinfection and liver and/or kidney transplant recipients are warranted.

Keywords:

• asunaprevir
• daclatasvir
• direct-acting antiviral
• hepatitis C virus
• interferon-free treatment
• liver transplantation
• sustained virologic response

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

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

Key issues

• Asunaprevir, a second-generation NS3 protease inhibitor developed by Bristol-Myers Squibb, exhibits strong antiviral activity against replicons based on hepatitis C virus (HCV) genotypes 1, 4, 5 and 6, and relatively weak antiviral activity against replicons based on HCV genotypes 2 and 3.

• Asunaprevir in combination with daclatasvir as dual treatment can achieve an sustained virologic response of 90% in HCV genotype 1b patents, although its antiviral activity is weak for genotype 1a, and additional beclatasvir or pegylated-interferon/ribavirin administration is required to achieve an acceptable sustained virologic response for HCV genotype 1a.

• In dual treatment with asunaprevir and daclatasvir, the appearance of resistance-associated variants to asunaprevir (mainly D168A/E/N/T/V/Y) and to daclatasvir (mainly L31M/V/I or Y93H/N) is associated with virologic failure.

• Asunaprevir 100 mg twice daily in combination with daclatasvir 60 mg once daily was approved for the treatment of patients with chronic hepatitis C in Japan in September 2014 (first in the world).

• Asunaprevir in combination with daclatasvir as an interferon-free therapy can be safely and effectively administered for liver transplant recipients with recurrent hepatitis C, while cyclosporine should be changed to tacrolimus due to possible drug–drug interactions with asunaprevir.

• Studies of asunaprevir in combination with other direct-acting antivirals are warranted for the treatment of patients with HCV genotype 1 or 4 and renal impairment or end-stage renal disease under hemodialysis, HIV-coinfection and liver and/or kidney transplantation.

Notes