Faldaprevir for the Treatment of Hepatitis C

Abstract

The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection are combinations of direct-acting antivirals, and faldaprevir is one of the new generation of HCV NS3/4A protease inhibitors. At the end of 2013, the US Food and Drug Administration (FDA) approved the HCV NS3/4A protease inhibitor simeprevir and the HCV NS5B polymerase inhibitor sofosbuvir. Simeprevir or sofosbuvir in combination with pegylated interferon and ribavirin are available for clinical use. Faldaprevir, another HCV NS3/4A protease inhibitor that also has fewer adverse events than telaprevir or boceprevir, is under development. Of interest, faldaprevir in combination with pegylated interferon and ribavirin, and interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin provides high sustained virological response rates for HCV genotype 1 infection. The aim of this article is to review these data concerning faldaprevir. Faldaprevir in combination with pegylated interferon and ribavirin treatment appears to be associated with fewer adverse events than telaprevir or boceprevir in combination with pegylated interferon and ribavirin, and may be one of the therapeutic options for treatment-naive patients with HCV genotype 1. The interferon-free combination of faldaprevir and deleobuvir with ribavirin was effective for HCV genotype 1 infection and may hold promise for interferon-ineligible and interferon-intolerant patients.

An insight into the molecular characteristics of hepatitis C virus for clinicians

“… 40 Pegylated interferon plus ribavirin had been the standard of care (SOC) for hepatitis C over a decade. However, the combination regimen only achieved SVR in 40%-50% of genotype 1 HCV infected patients 41 , 42 worldwide despite the IL-28 genotype diversity in different nationalities. 43 The SVR might be higher in other genotypes, but still, more than a quarter of patients were non-responders.…”

Identification of a New Drug Binding Site in the RNA-Dependent-RNA-Polymerase (RdRp) Domain

“…Cell-based assays have shown antiviral activity of these drugs in SARS-CoV-2 [49,50]. Hepatitis C NS3 protease inhibitors asunaprevir and faldaprevir were the top antivirals identified from our Set 2 dockings [51,52]. NS3 is a serine protease required for proteolytic cleavage of the HCV polyprotein [51,53].…”

“…It is possible these sites share a common structural arrangement of electrostatic surfaces for sirolimus binding because polyanionic sulphated naphthylamine derivatives such as suramin and Evans Blue bind to positively charged patches of SARS-CoV-2 RdRp [55]. Suramin binds two sites and prevents binding of the RNA template and Hepatitis C NS3 protease inhibitors asunaprevir and faldaprevir were the top antivirals identified from our Set 2 dockings [51,52]. NS3 is a serine protease required for proteolytic cleavage of the HCV polyprotein [51,53].…”

Identificación de los polimorfismos rs12979860 y rs8099917 de IL28B en el diagnóstico, control y determinación de tratamiento en pacientes venezolanos infectados con el virus de hepatitis C.

“…Sin embargo, el acceso al tratamiento contra el VHC está mejorando debido a que los precios de estos medicamentos han disminuido drásticamente gracias a la introducción de versiones genéricas, pero su disponibilidad sigue siendo limitada en muchos países. Un ensayo de clínico reciente, en fase 2b, aleatorizado con faldaprevir (inhibidor de la proteasa NS3 / 4A) y deleobuvir (inhibidor de la polimerasa NS5B), demostró que pacientes que tenían el alelo CC del polimorfismo rs12979860 tenían tasas de RVS más elevadas en comparación a pacientes sin este alelo, sugiriendo que la inmunidad innata aún puede ser importante y el genotipo IL28B puede afectar la eficacia del tratamiento en ciertos regímenes sin IFN (33)(34)(35)(36).…”