Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir: A Review in Chronic HCV Genotype 1 Infection

Abstract

A fixed-dose tablet comprising ombitasvir (an NS5A replication complex inhibitor), paritaprevir (an NS3/4A protease inhibitor) and ritonavir (a cytochrome P450 inhibitor) taken in combination with dasabuvir (an NS5B polymerase inhibitor) is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in several countries, including the USA (copackaged as Viekira Pak(™)) and those of the EU (Viekirax(®) and Exviera(®)). In phase II and III trials, this interferon-free regimen, taken ± ribavirin, provided high rates of sustained virological response 12 weeks post-treatment in adults with chronic HCV genotype 1a or 1b infection, including those with compensated cirrhosis, liver transplants or HIV-1 co-infection. The regimen was generally well tolerated, with nausea, insomnia, asthenia, pruritus, other skin reactions and fatigue being among the most common tolerability issues. Thus, ombitasvir/paritaprevir/ritonavir plus dasabuvir is an effective interferon-free, direct-acting antiviral regimen for use ± ribavirin in a broad range of adults chronically infected with HCV genotype 1.

Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: Real‐world data from a large healthcare provider

“…One of the new regimens includes a fixed‐dose tablet comprising ombitasvir (NS5A replication complex inhibitor), paritaprevir (NS3/4A protease inhibitor; identified by AbbVie and Enanta) and ritonavir (cytochrome P450 inhibitor), which is taken in combination with dasabuvir (NS5B polymerase inhibitor). The combined regimen (OPrD), taken with or without ribavirin, is indicated for chronic HCV GT1 patients in several countries, including in the USA and in Europe …”

“…A pooled analysis of 581 GT1b patients across 5 clinical trials reports that SVR‐12 rates with OBV/PTV/r+DSV for 12 weeks were 100% (60/60) and 99% (515/521) in patients with and without cirrhosis, respectively. Adverse events were typically mild, such as fatigue, headache, nausea and diarrhoea …”

Clopidogrel Increases Dasabuvir Exposure With or Without Ritonavir, and Ritonavir Inhibits the Bioactivation of Clopidogrel

“…Dasabuvir, a nonstructural protein 5B inhibitor, is part of a novel four‐drug (3D) regimen for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection, which affects more than 80 million people worldwide . The drug–drug interaction (DDI) potential of the dasabuvir, paritaprevir/ritonavir, and ombitasvir regimen has been characterized as a part of the marketing approval process, but the compounds are yet individually understudied in this regard .…”

The Combination of Grazoprevir, a Hepatitis C Virus (HCV) NS3/4A Protease Inhibitor, and Elbasvir, an HCV NS5A Inhibitor, Demonstrates a High Genetic Barrier to Resistance in HCV Genotype 1a Replicons

“…The introduction of direct-acting antiviral agents (DAAs) as add-ons to the previous standard of care (SOC) consisting of pegylated interferon alpha plus ribavirin (PR) significantly improved sustained virologic response (SVR) rates from 40 to 50% to 65 to 70% in the previously hard-to-cure genotype 1 (GT1) patients after a 24-to 48-week treatment course. Further treatment advancements have been achieved with the introduction of interferon-free all-oral DAAs, with SVR rates now in excess of 90% after 12 weeks of therapy for GT1 patients (4,5,6). Recent reports indicate that therapy can be further simplified and likely shortened to Ͻ12 weeks in some cases while maintaining high SVR rates.…”