Sustained Virologic Response Rate of 96% in HCV Genotype 1a-Infected Patients Treated With Ombitasvir/Paritaprevir/r and Dasabuvir With Ribavirin

Abstract

Introduction: The interferon-free 3 direct-acting antiviral (3D) regimen of ombitasvir (an NS5A inhibitor), paritaprevir (an HCV NS3/4A protease inhibitor identified by AbbVie and Enanta, boosted with ritonavir [r]) and dasabuvir (a non-nucleoside NS5B RNA polymerase inhibitor) is approved to treat patients infected with HCV genotype (GT) 1. Using pooled data from four phase 3 studies in treatmentnaïve and prior pegIFN/RBV-experienced patients with GT1a infection, with or without cirrhosis, we report the safety and efficacy in patients who received the label-recommended 3D regimen plus ribavirin (RBV). Methods: Genotype 1a-infected patients from the PEARL-IV, SAPPHIRE-I, SAPPHIRE-II, and TUR-QUOISE-II studies were included in this post-hoc analysis. Efficacy was assessed by the proportion of patients achieving sustained virologic response (HCV RNA < 25 IU/mL) 12 weeks after completion of treatment (SVR12). Per the US Prescribing Information and European SmPC, the label-recommended regimen for GT1a infection is 3D+RBV for 12 weeks in non-cirrhotic patients, and 3D+RBV for 24 weeks in patients with cirrhosis. Adverse events (AEs) and laboratory measures are reported for all patients receiving the label-recommended regimen. Results: Among 714 HCV GT1a-infected patients treated with the label-recommended 3D+RBV regimen, 64% were male, 33% were treatment-experienced, 17% had cirrhosis, and 85% had baseline viral loads ≥800,000 IU/mL. Sustained virologic response was achieved in 96% (95% CI, 94-97%) of patients (Table). Response rates were similar regardless of the presence or absence of cirrhosis (95 versus 96%, respectively). Virologic failure was observed in 18 (2.5%) patients, 5 (0.7%) with on-treatment breakthrough and 13 (1.8%) with post-treatment relapse. Seven patients (1.0%) discontinued treatment due to AEs, 4 of whom subsequently achieved SVR12. The most common AEs were fatigue (41%), headache (33%), nausea (23%), and insomnia (17%). Grade 3+ laboratory abnormalities were infrequent for ALT (0.9%), AST (0.6%), hemoglobin (0.3%), and total bilirubin (2.8%). Conclusion: In HCV GT1a-infected patients, the label-recommended 3D regimen with RBV achieved high SVR12 rates, including historically difficult-to-cure subgroups of patients with prior PR null response and/or cirrhosis.Table 1