Sofosbuvir in Treatment-Naïve Patients with Hepatitis C Infection
Background: In phase 2 trials, treatment with the nucleotide polymerase inhibitor sofosbuvir resulted
in high sustained virologic response in patients with chronic genotype (GT) 1, 2, or 3 hepatitis C virus
(HCV) infection.
Methods: We conducted two phase 3 studies in treatment-naïve patients infected with HCV. In the
NEUTRINO study, patients with HCV GT 1, 4, 5, or 6 infection received open-label sofosbuvir 400
mg plus peginterferon alfa-2a 180 µg weekly and ribavirin 1000-1200 mg daily for 12 weeks. In the
FISSION study, patients with HCV GT 2 or 3 infection were randomly assigned to receive sofosbuvir
400 mg daily and ribavirin 1000-1200 mg daily for 12 weeks or peginterferon alfa-2a 180 µg weekly
and ribavirin 800 mg for 24 weeks. The primary endpoint in both studies was the proportion of
patients with a SVR 12 weeks after therapy.
Results:
In the NEUTRINO study, 327 patients (89% GT 1, 9% GT 4, <1% GT 5, and 2% GT 6) were enrolled
and received study drug; 64% were male, 17% had compensated cirrhosis, and 29% carried the IL28B
CC genotype. In the FISSION study, 256 patients (27% GT 2 and 71% GT 3) were randomized to
receive SOF +RBV and 243 (28% GT 2 and 72% GT 3) were randomized to receive PEG + RBV;
Overall, 66% were male, 20% had compensated cirrhosis, and 43% carried the IL28B CC genotype.
Rates of SVR12 are given in table. One on-treatment breakthrough was observed in a SOF+RBV
patient with documented non-adherence. No S282T was observed in patients with relapse.
Sofosbuvir was generally well tolerated with lower rates of the most common adverse events fatigue, headache, nausea, and insomnia - observed in patients receiving sofosbuvir and ribavirin than
in those receiving peginterferon and ribavirin.
Conclusions: Twelve weeks of sofosbuvir combination therapy was well tolerated and associated
with high rates of SVR in treatment-naïve patients with HCV genotype 1-6 infection.
Table 1. Outcomes
Response
SVR12
GT 2
GT 3
Non-cirrhotic
Cirrhotic
On-Treatment VF
Relapse
NEUTRINO
SOF+PEG+RBV for 12
wk (n = 327)
91%
n/a
n/a
92%
80%
0
9%
FISSION
SOF+RBV for 12 wk
PEG+RBV for 24 wk
(n = 253)
(n = 243)
67%
67%
97%
78%
56%
63%
72%
74%
47%
38%
<1%
7%
30%
21%
VF=virologic failure; on-treatment virologic failure includes non-response and breakthrough