It is estimated that the response rate in patients who previously failed pegylated interferon and ribavirin therapy will approximate the observed response rate in NEUTRINO subjects with multiple baseline factors traditionally associated with a lower response to interferon-based treatment (Table 9). The SVR rate in the NEUTRINO trial in genotype 1 subjects with IL28B non-C/C alleles, HCV RNA >800,000 IU/mL and Metavir F3/F4 fibrosis was 71% (37/52).

Clinical Trials in Subjects with Genotype 2 or 3 CHC

Treatment-Naïve Adults ─ FISSION (Study 1231)
FISSION was a randomized, open-label, active-controlled trial that eva luated 12 weeks of treatment with SOVALDI and ribavirin compared to 24 weeks of treatment with peginterferon alfa 2a and ribavirin in treatment-naïve subjects with genotype 2 and 3 HCV. The ribavirin doses used in the SOVALDI + ribavirin and peginterferon alfa 2a + ribavirin arms were weight-based 1000-1200 mg per day and 800 mg per day regardless of weight, respectively. Subjects were randomized in a 1:1 ratio and stratified by cirrhosis (presence vs. absence), HCV genotype (2 vs. 3) and baseline HCV RNA level (<6 log10IU/mL vs. ≥6 log10IU/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 per mL; 20% had cirrhosis; 72% had HCV genotype 3.  Table 10 presents the response rates for the treatment groups of SOVALDI + ribavirin and peginterferon alfa + ribavirin.

Table 10         Response Rates in Study FISSION

 SOVALDI + RBV 12 weeks
 Peg-IFN alfa + RBV 24 weeks
 
 N=256a
 N=243a
 
Overall SVR
 67% (171/256)
 67% (162/243)
 
Treatment  differenceb
 0.3% (95% CI: -7.5% to 8.0%)
 
 Genotype 2
 95% (69/73)
 78% (52/67)
 
 Genotype 3
 56% (102/183)
 63% (110/176)
 
Outcome for subjects without SVR
 
On-treatment virologic failure
 <1% (1/256)
 7% (18/243)
 
Relapsec
 30% (76/252)
 21% (46/217)
 
  Genotype 2
 5% (4/73)
 15% (9/62)
 
  Genotype 3
 40% (72/179)
 24% (37/155)
 
Otherd
 3% (8/256)
 7% (17/243)
 
a.         Including three subjects with recombinant genotype 2/1 HCV infection.
b.         Adjusted for pre-specified stratification factors.
c.         The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment.
d.         Other inclu