All-oral, fixed-dose combination therapy with daclatasvir/asunaprevir/BMS-791325 for noncirhotic patients with chronic HCV genotype 1 infection: UNITY-1 phase 3 SVR12 results.

Abstract

Introduction: The all-oral combination of daclatasvir (DCV; pangenotypic NS5A inhibitor), asunaprevir (ASV; NS3 protease inhibitor), and BMS-791325 (non-nucleoside NS5B inhibitor) - DCV 3DAA regimen - was evaluated without ribavirin in HCV genotype (GT) 1-infected treatment-naive and -experienced patients without cirrhosis in a Phase 3, open-label, international clinical trial. Method(s): Patients received a fixed-dose combination (FDC) of DCV 30 mg, ASV 200 mg, and BMS-791325 75 mg twice daily for 12 weeks. SVR12 rates in the treatment-naive and -experienced cohorts were evaluated separately as key efficacy outcomes. Result(s): SVR12 was achieved by 92% of treatment-naive patients (Table). Among treatment-experienced patients, 89% achieved SVR12. Virologic failure occurred in 34 (8%) patients overall. Baseline characteristics were comparable between the treatment-naive (N=312) and treatment- experienced (N=103) cohorts. Overall, patients were 58% male and 26% IL28B (rs1297860) CC genotype; 73% were infected with GT 1a and 27% with GT 1b. One death reported posttreatment was considered not related to study treatment. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 (<1%) adverse events leading to treatment discontinuation. The most common adverse events (in >10% of patients) were headache, fatigue, diarrhea, and nausea. Conclusion(s): In this Phase 3 study of 415 patients, 12 weeks of alloral treatment with DCV/ASV/BMS-791325 FDC achieved high SVR12 rates in patients with chronic HCV GT 1 infection and was well tolerated. These findings demonstrate the potent antiviral activity, safety, and tolerability of the DCV 3DAA regimen in treatment-naive and treatmentexperienced patients without cirrhosis. [TABLE PRESENTED].