Sofosbuvir is an oral nucleotide prodrug which inhibits the HCV-specific NS5B RNA polymerase, thereby acting as a chain terminator and preventing viral replication.1
The safety and efficacy of sofosbuvir (400mg once daily) together with ribavirin (1g [<75kg] or 1.2g [≥75kg] daily in divided doses) with or without peginterferon alfa-2a (180 microgram by subcutaneous injection once weekly) were assessed in clinical studies involving 1,568 patients with chronic hepatitis. In all studies, the sustained virologic response was assessed at 12 weeks after the end of treatment.1
Patients without treatment options
Genotype 2 or 3
Two phase III studies were conducted to assess the efficacy of sofosbuvir plus ribavirin in patients with hepatitis C virus (HCV) genotype 2 or 3 infection for whom peginterferon was unsuitable (POSITRON, n=278) or who had not responded to prior interferon treatment (FUSION, n=201).2
In the POSITRON study, the rate of sustained virologic response following 12 weeks of treatment was 78% (95% CI 72−83) in the sofosbuvir-ribavirin group compared with 0% in the placebo group (p<0.001).2
In the FUSION study, the rate of sustained virologic response was 50% (95% CI 40–60) after 12 weeks of treatment and 73% (95% CI 63–81) after 16 weeks of treatment (difference, -23 percentage points [95% CI -35 to -11; p<0.001).2
In both studies, responses occurred more frequently among patients with HCV genotype 2 infection than among those with genotype 3 infection and among genotype 3 patients without cirrhosis than among those with cirrhosis.2
Genotype 1, 4, 5 or 6
In the phase III open-label NEUTRINO study, 327 patients with previously untreated hepatitis C genotype 1, 4, 5 or 6 infection received sofosbuvir, ribavirin and peginterferon alfa-2a for 12 weeks.3
In total, 90% of patients achieved a sustained virologic response (95% CI 87−93). Response rates did not differ greatly according to HCV genotype.3
Genotype 2 or 3
In another phase III open-label study (FISSION, n=499) patients with HCV genotype 2 or 3 infection were randomised to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin (800mg daily in two divided doses) for 24 weeks.3
The rate of sustained virologic response was 67% in both groups, demonstrating non-inferiority of the sofosbuvir-ribavirin regimen to the peginterferon-ribavirin regimen. In both groups, response rates were higher among patients with genotype 2 infection than in those with genotype 3 infection (97% vs 56% in the sofosbuvir group and 78% vs 63% in the peginterferon group).3
The efficacy of a sofosbuvir-ribavirin regimen in patients with HIV/HCV co-infection already receiving antiretroviral therapy was assessed in the open-label PHOTON-1 study. Treatment duration was 24 weeks in genotype 1 patients (n=114) and 12 weeks in genotype 2 (n=26) and 3 (n=42) patients; all patients were treatment-naive.4
A sustained virologic response was observed in 76%, 88% and 67% of genotype 1, 2 and 3 patients, respectively.4
Treatment-naive and previously treated patients
Genotype 2 or 3
The placebo-controlled VALENCE study investigated the efficacy of a sofosbuvir-ribavirin regimen administered for 12 weeks in patients with HCV genotype 2 infection (n=73) and for 12 or 24 weeks in patients with HCV genotype 3 infection (n=11 and n=250, respectively). Both treatment-naive and treatment-experienced patients were included.5
A sustained virologic response was observed in 93% of genotype 2 patients and in 85% of genotype 3 patients treated for 24 weeks. In total, 27% of genotype 3 patients treated for 12 weeks achieved a sustained virologic response.5
Treatment with sofosbuvir was generally well tolerated in clinical studies, with low rates of treatment discontinuation due to adverse events.1
The safety profile in patients co-infected with HCV/HIV was similar, with no decrease in CD4 T-cell percentage observed.4
- Sovaldi Summary of Product Characteristics, January 2014.
- Jacobson IM et al. N Engl J Med 2013; 368: 1867-77.
- Lawitz E et al. N Engl J Med 2013; 368: 1878-87.
- Sulkowski M et al. Poster presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases. Washington DC, US. November 2013.
- Zeuzem S et al. Poster presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases. Washington DC, US. November 2013.
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