Dasabuvir is a non-nucleoside inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome.
Ombitasvir and paritaprevir are inhibitors of HCV NS5A and NS3/4A protease, respectively, both of which are essential for viral replication. Ritonavir is not active against HCV but is a CYP3A inhibitor included to increase systemic exposure of paritaprevir.
Exviera is currently licensed for use only in combination with Viekirax for patients with HCV genotype 1, with or without ribavirin. Viekirax is also licensed for HCV genotype 4 in combination with ribavirin. Both drugs are used for 12 or 24 weeks, depending on the viral genotype and the extent of liver damage.
The efficacy of dasabuvir in combination with ombitasvir/paritaprevir/ritonavir with or without ribavirin was evaluated in four phase III trials involving 1,083 subjects (including 189 with compensated cirrhosis) who received the recommended regimen for their HCV genotype 1 subtype, cirrhosis status and relevant baseline characteristics. In a pooled analysis of these studies, 97% achieved a sustained virologic response (defined as unquantifiable or undetectable HCV RNA 12 weeks after the end of treatment).
In clinical studies of subjects receiving dasabuvir plus ombitasvir/paritaprevir/ritonavir with ribavirin the most commonly reported adverse effects were fatigue and nausea. Overall, 0.2% of patients interrupted treatment due to adverse effects and 0.2% discontinued treatment permanently.