Faldaprevir for the treatment of genotype-1 hepatitis C virus

Abstract

Historically, pegylated interferon in combination with ribavirin was the standard of care in hepatitis C virus; however, this combination is often poorly tolerated, has a significant side-effect profile and is of limited efficacy in hepatitis C virus genotype-1. More recently, pegylated interferon/ribavirin has been combined with direct acting antiviral agents such as the first generation NS3/4A protease inhibitors. Faldaprevir, a first generation, second-wave protease inhibitor, when used with a pegylated interferon/ribavirin regimen, has also been shown to increase treatmentsuccess while shortening treatment duration; however, second generation direct acting antiviral agents offer even betterefficacy and tolerability. Various direct acting antiviral agent combinations in interferon-free regimens have been effective in over 95% of patients and are now in licensed use. While faldaprevir was a pioneering drug, by the time it reached late phase development it was superseded by newer agents.

Keywords:

• boceprevir
• faldaprevir
• hepatitis C
• liver transplantation
• pegylated interferon
• ribavirin
• simeprevir
• telaprevir

Financial & competing interests disclosure

K Agarawal and A Barnabas have been principle investigators and subinvestigators in clinical trials of faldaprevir, respectively. 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

• Faldaprevir, a protease inhibitor, showed initial promise as a potent DAA for the treatment of hepatitis C, when used in combination with PEG IFN/riba.

• From phase 2 and 3 trial clinical data, however, it emerged that competing direct acting antiviral agents offer significant advantages in terms of both tolerability and efficacy.

• Further trial data showed that in interferon-free regimens incorporating faldaprevir, efficacy appeared to be inferior to emerging DAAs.

• Further development of faldaprevir was discontinued on 20 June 2014.