PS 1-3: Daclatasvir Plus Sofosbuvir ± Ribavirin for Treating Chronic HCV Infection in Patients with Advanced Liver Disease: European Compassionate Use Program Results

Aims: The all-oral, pan-genotypic combination of daclatasvir+sofosbuvir± ribavirin (DCV+SOF±RBV) demonstrated high sustained virologic response rates at posttreatment Week 12 (SVR12) in phase 3 studies of patients with chronic HCV. We report efficacy and safety results from a large European compassionate use program that provided DCV+SOF±RBV therapy to patients with chronic HCV infection and severe liver disease. Methods: Eligible patients were adults with chronic HCV infection at a high risk of hepatic decompensation or death within 12 months if left untreated, or urgent need of viral clearance due to extrahepatic manifestations or comorbidities, and with no available treatment options. Patients received DCV(60mg)+SOF(400mg) once daily for 24 weeks; RBV addition or reduced treatment duration was the physician’s choice. The primary efficacy outcome was SVR12. Results: Efficacy data were available for 436/485 patients enrolled. Most patients were HCV treatment experienced (70%) with mean HCV RNA 5.5 log10 IU/mL. 388 (80%) patients had confirmed cirrhosis( Child-Pugh class B or C, 165 (43%); MELD scores>15, 37 (10%)) , 87 patients (18%) had received liver transplants and 55 (11%) were HIV/HCV coinfected. SVR12 was achieved by 394/436 (90%) patients (table). There were 13 relapses and 1 on-treatment virologic failure. SVR12 rates were similar with/without ribavirin and comparable across HCV GT, presence of cirrhosis, liver transplant status, HIV coinfection, and other baseline characteristics. There were 28 deaths over treatment or follow-up (none considered treatment-related), 91 experienced serious adverse events (11 considered treatment-related), and 38 discontinued treatment or died due to adverse events (10 treatment- related). Most deaths and serious adverse events were directly or indirectly associated with advanced liver disease. Adverse events (any grade) occurring in ≥5% of patients were fatigue, anaemia, headache, nausea, and diarrhoea. Conclusions: The all-oral regimen of DCV+SOF±RBV was highly effective and well tolerated in this large European real-world cohort of patients with advanced liver disease.