Daclatasvir + sofosbuvir + ribavirin for HCV GT-3 with cirrhosis or advanced fibrosis: ALLY-3 + study.

Abstract

Background: HCV GT3-infected patients are a challenging population in urgent need of optimally effective therapies. A previous study (ALLY-3) in GT-3 infection achieved 96 % SVR12 in patients without cirrhosis, and 63 % in patients with cirrhosis, following 12 weeks of daclatasvir (DCV) + sofosbuvir (SOF). ALLY- 3 + evaluated DCV + SOF + ribavirin (RBV) for 12 or 16 weeks in HCV GT-3 with advanced fibrosis/cirrhosis. Method(s): Open-label, phase 3b study in GT-3 treatment-naive or - experienced adults with compensated advanced fibrosis or cirrhosis. Patients were randomized 1:1 to 12 or 16 weeks of DCV (60 mg QD) + SOF (400 mg QD) + RBV (weight-based), stratified by advanced fibrosis/cirrhosis status. Interim efficacy (SVR4) and safety outcomes are reported. SVR12 (primary endpoint) data will be available for presentation. Result(s): 50 patients were treated. Most were male (80 %), white (98 %), and treatment-experienced (74 %; 10 % prior relapse on SOF + RBV); 72 % had cirrhosis, and 52 % had HCV-RNA >=6 million IU/mL. Overall SVR4 by intention-to-treat analysis was 92 %. SVR4 in the 12-week arm was 88 % (cirrhosis 83 %, advanced fibrosis 100 %) and in the 16-week arm was 96 % (cirrhosis 94 %, advanced fibrosis 100 %; Figure); 4/5 (80 %) with prior relapse on SOF + RBV achieved SVR4. There were 3 relapses, no virologic breakthroughs, and 1 treatment-unrelated death. Treatment was well tolerated-the most common adverse events (AEs) were insomnia (30 %), fatigue (26 %) and headache (24 %). There were no discontinuations for AEs. Conclusion(s): DCV + SOF + RBV for 12 or 16 weeks achieved high SVR4 rates of 88 and 96 %, respectively in HCV GT3-infected patients with compensated advanced fibrosis/cirrhosis, and was generally well tolerated. (Figure Presented).