EASL 2013 Abstract #1411: Sofosbuvir + Peginterferon + Ribavirin for 12 Weeks Achieves 90% SVR12 in Genotype 1, 4, 5, OR 6 HCV Infected Patients: The NEUTRINO Study

CARE Liver Disease Faculty Canadian Perspectives from EASL 2013

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Background: 327 patients (292 genotype 1, 28 genotype 4, 7 genotype 5/6) were enrolled and received study drug; 64% were male, 17% Black, 17% had compensated cirrhosis, and 29% carried the IL28B CC genotype. The SVR12 rate for SOF + PEG-IFN + RBV (295/327, 90%) was superior to a historic control rate of 60% (p < .001). SVR12 rates for subgroups are shown in the table below. All patients had HCV RNA < LLOQ by treatment week six and relapse accounted for all virologic failures. No NS5B S282T variants were detected following relapse. Five patients (2%) discontinued treatment due to AEs and four patients (1%) experienced SAEs. AEs and laboratory abnormalities were consistent with the profile for PEG-IFN+RBV. AEs observed in ≥ 20% included fatigue, headache, nausea, insomnia and anemia.

Conclusions/Key Take Away: 12 weeks of treatment with SOF + PEG-IFN + RBV achieved 90% SVR12 in treatment-naïve genotype 1, 4, 5, or 6 HCV-infected patients with no viral resistance detected in failures. This regimen was well tolerated and is a short, simple and effective treatment option for patients with genotype 1, 4, 5, or 6 HCV infection.


Abstract 1417: Sustained Virologic Response With Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) in Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) or Boceprevir (BOC)

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Results: Most patients had HCV GT1a (83%), were IL28B non-CC (98%), and had estimated METAVIR stage ≥F2 (83%). Mean HCV RNA was ≥ 6 log IU/mL. HCV RNA < 25 IU/mL was achieved in 40/41 patients by week four and in all patients by end of treatment. None had breakthrough or relapse and all patients achieved SVR4 (Table). The most common adverse events (> 30% total) were fatigue and headache. There were no Grade 3–4 hematologic or hepatic laboratory abnormalities.

Conclusions/Key Take Away: The all-oral, once-daily combination of DCV + SOF with or without RBV for 24 weeks achieved 100% SVR4 in non-cirrhotic GT1 prior TVR/BOC treatment failures. These data provide proof-of-concept that the combination of two potent direct-acting antivirals (DAAs) with different viral targets is effective in patients who failed PEG-IFN/RBV + a protease inhibitor (PI).

The Canadian availability of sofosbuvir—a nucleotide polymerase inhibitor with pan-genotypic activity—is eagerly anticipated. Data from the NEUTRINO trial confirm its effectiveness and safety when combined with PEG-IFN/RBV for only 12 weeks in naïve patients with non-2/3 genotypes, including difficult-to-cure subgroups (e.g., 80% SVR in cirrhotics). As we accumulate more patients who have failed treatment with the first generation PIs—the majority of whom have resistance mutations around the catalytic site of the NS3/4A serine protease—additional treatment options are necessary. Data from the small AI444040 study demonstrate proof-of-concept that an IFN-free regimen including two potent DAAs with different viral targets may be an effective salvage therapy for these patients.
— CARE Liver Disease Faculty