European Association for the Study of the Liver (EASL) 2015
EASL 2015. Late-breaking Oral 8. Daclatasvir, Sofosbuvir, and Ribavirin Combination for HCV Patients with Advanced Cirrhosis or Post-Transplant Recurrence: Phase 3 ALLY-1 Study
F. Poordad et al.
CARE Faculty Perspective:
ALLY-1 is a multicentre, open label, phase 3 study examines the efficacy of Daclatasvir (DCV), sofosbuvir (SOF) and ribavirin (RBV) in HCV infected patients who either had advanced cirrhosis, or those who were post-liver transplant. Although all genotypes could be enrolled in the study, the primary endpoint was SVR12 in genotype 1 patients. Both treatment naïve (TN) and treatment experienced (TE) patients were enrolled, and DAA failures were allowed, except for patients who had had previous exposure to NS5A inhibitors. Patients were randomized to receive 12 weeks of treatment with DCV 60mg daily, SOF 400 mg daily and RBV (dosage starting at 600mg/day, increased to 1000mg/day based on anemia and renal function). Patients who had treatment interruption due to a liver transplant were eligible to receive an additional 12 weeks of treatment immediately post-transplant.
There were 60 patients in the advanced cirrhosis cohort, and 53 patients in the post-transplant cohort. Of those in the cirrhosis cohort, the majority (72%) were genotype 1 (G1) and 40% were TN. The MELD in this cohort ranged from 8 to 27, 20% were Child-Pugh A (CTPA), 53% were CTPB, and 27% were CTPC. In the post-transplant cohort, 77% were G1 and 42% were TN. 4 patients had a transplant during the course of the study – all of these patients had hepatocellular carcinoma, and 2 of these patients had detectable viral load at the time of transplant.
The overall SVR12 rates were 83% for the advanced cirrhotic cohort, compared to 94% for the post-transplant population. The primary endpoint (SVR12 in G1) was 82% in the cirrhotic group, and 95% for the transplant group. A regression analysis revealed that neither gender, age, IL28B status, nor baseline RNA levels affected SVR12. Relapse was seen in 9 patients in the cirrhosis group, with another patient in this group having a detectable RNA at EOT, and 3 patients in the transplant group. Patients with CTPC were found to have the lowest SVR rates (92% in CTPA, 94% in CTPB, and 56% in CTPC patients - See Figure 1), with the greatest determinant of failure in the latter group being an albumin <2.8g/dL. SVR12 rates in genotype 3 patients were 83% in the cirrhosis group and 91% in the transplant group.
The regimen was well tolerated, with the most common adverse events being headache and fatigue, with a favourable drug-drug interaction profile in the post-transplant patients.
These data suggest that this 12-week regimen is safe and well tolerated across multiple genotypes, although SVR 12 rates may be lower in advanced disease (CTPC patients). SVR12 rates ranged from 84-95% across the various groups, and there was no drug-drug interaction with immunosuppressive medications. This combination of medications may be highly effective in G3 patients with advanced disease.
- CARE Liver Disease Faculty