27/28 patients with genotype 4 HCV achieved SVR12. A single subject with genotype 5 and all 6 subjects with genotype 6 HCV infection in this study achieved SVR12.

Clinical studies in subjects with genotype 2 and 3 chronic hepatitis C

Treatment-naïve adults - FISSION (study 1231)

FISSION was a randomised, open-label, active-controlled study that eva luated 12 weeks of treatment with sofosbuvir and ribavirin compared to 24 weeks of treatment with peginterferon alfa 2a and ribavirin in treatment-naïve subjects with genotype 2 or 3 HCV infection. The ribavirin doses used in the sofosbuvir + ribavirin and peginterferon alfa 2a + ribavirin arms were weight-based 1,000-1,200 mg/day and 800 mg/day regardless of weight, respectively. Subjects were randomised in a 1:1 ratio and stratified by cirrhosis (presence versus absence), HCV genotype (2 versus 3) and baseline HCV RNA level (<6 log10 IU/mL versus≥6 log10 IU/mL). Subjects with genotype 2 or 3 HCV were enrolled in an approximately 1:3 ratio.

Treated subjects (n = 499) had a median age of 50 years (range: 19 to 77); 66% of the subjects were male; 87% were White; 3% were Black; 14% were Hispanic or Latino; mean body mass index was 28 kg/m2 (range: 17 to 52 kg/m2); 57% had baseline HCV RNA levels greater than 6 log10 IU/mL; 20% had cirrhosis; 72% had HCV genotype 3. Table 7 presents the response rates for the treatment groups of sofosbuvir + ribavirin and peginterferon alfa + ribavirin.

Table 7: Response rates in study FISSION

  SOF+RBV

12 weeks

(n = 256)a
 PEG+RBV

24 weeks

(n = 243) 
 
Overall SVR12
 67% (171/256)
 67% (162/243)
 
Genotype 2
 95% (69/73)
 78% (52/67)
 
Genotype 3
 56% (102/183)
 63% (110/176)
 
Outcome for subjects without SVR12
    
On-treatment virologic failure
 <1% (1/256)
 7% (18/243)
 
Relapseb
 30% (76/252)
 21% (46/217)
 
Otherc
 3% (8/256)
 7% (17/243)
 
a. The efficacy analysis includes 3 subjects with recombinant genotype 2/1 HCV infection.

b. The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment.

c. Other includes subjects who did not achieve SVR12 and did not meet virologic failure criteria (e.g., lost to follow-up).

The difference in the overall SVR12 rates between sofosbuvir + ribavirin and peginterferon alfa + ribavirin treatment groups was 0.3% (95% confidence interval: -7.5% to 8.0%) and the study met the predefined non-inferiority criterion.

Response rates for subjects with cirrhosis at baseline are presented in Table 8 by HCV genotype.

Table 8: SVR12 rates by cirrhosis and genotype in study FISSION

  Genotype 2
 Genotype 3
 
SOF+RBV

12 weeks

(n = 73)a
 PEG+RBV