74); 60% of the subjects were male; median body mass index was 25 kg/m2 (range: 17 to 44 kg/m2); the mean baseline HCV RNA level was 6.4 log10 IU/mL; 21% had cirrhosis; 78% had HCV genotype 3; 65% were prior relapsers. Table 13 presents the response rates for the treatment groups of sofosbuvir + ribavirin for 12 weeks and 24 weeks.
Placebo recipients are not included in the tables since none achieved SVR12.
Table 13: Response rates in study VALENCE
Genotype 2
SOF+RBV 12 weeks
(n = 73)
Genotype 3
SOF+RBV 12 weeks
(n = 11)
Genotype 3
SOF+RBV 24 weeks
(n = 250)
Overall SVR12
93% (68/73)
27% (3/11)
84% (210/250)
Outcome for subjects without SVR12
On-treatment virologic failure
0% (0/73)
0% (0/11)
0.4% (1/250)
Relapsea
7% (5/73)
55% (6/11)
14% (34/249)
Otherb
0% (0/73)
18% (2/11)
2% (5/250)
a. The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment.
b. Other includes subjects who did not achieve SVR12 and did not meet virologic failure criteria (e.g., lost to follow-up).
Table 14 presents the subgroup analysis by genotype for cirrhosis and exposure to prior HCV treatment.
Table 14: SVR12 rates for selected subgroups by genotype in study VALENCE
Genotype 2
SOF+RBV 12 weeks
(n = 73)
Genotype 3
SOF+RBV 24 weeks
(n = 250)
Treatment-naïve
97% (31/32)
93% (98/105)
Non-cirrhotic
97% (29/30)
94% (86/92)
Cirrhotic
100% (2/2)
92% (12/13)
Treatment-experienced
90% (37/41)
77% (112/145)
Non-cirrhotic
91% (30/33)
85% (85/100)
Cirrhotic
88% (7/8)
60% (27/45)
SVR12 to SVR24 concordance
The concordance between SVR12 and SVR24 (SVR 24 weeks after the end of the treatment) following treatment with sofosbuvir in combination with ribavirin or ribavirin and pegylated interferon demonstrates a positive predictive value of 99% and a negative predictive value of 99%.
Clinical efficacy and safety in special populations
HCV/HIV co-infected patients - PHOTON-1 (study 123)
Sofosbuvir was studied in an open-label clinical study eva luating the safety and efficacy of 12 or 24 weeks of treatment with sofosbuvir and ribavirin in subjects with genotype 1, 2 or 3 chronic hepatitis C co-infected with HIV-1. Genotype 2 and 3 subjects were either treatment-naïve or experienced, whereas genotype 1 subjects were naïve to prior treatment. Treatment duration was 12 weeks in treatment-naïve subjects with genotype 2 or 3 HCV infection, and 24 weeks in treatment-experienced subjects with genotype 3 HCV infection, as well as subjects with genotype 1 HCV infection. Subjects received 400 mg sofosbuvir and weight-based ribavirin (1,000 mg for subjects weighing <75 kg or 1,200 mg for subjects weighing ≥75 kg). Subjects were either not on antiretroviral therapy with a CD4+ cell count >500 cells/mm3 or had virologically suppressed HIV-1 with a CD4+ cell count >200 cells/mm3. 95% of patients received antiretroviral therapy at the time of enrolment.
