24 weeks

(n = 67) 
 SOF+RBV

12 weeks

(n = 183) 
 PEG+RBV

24 weeks

(n = 176) 
 
Cirrhosis
        
No
 97% (59/61)
 81% (44/54)
 61% (89/145)
 71% (99/139)
 
Yes
 83% (10/12)
 62% (8/13)
 34% (13/38)
 30% (11/37)

a. The efficacy analysis includes 3 subjects with recombinant genotype 2/1 HCV infection.

Interferon intolerant, ineligible or unwilling adults - POSITRON (study 107)

POSITRON was a randomised, double-blinded, placebo-controlled study that eva luated 12 weeks of treatment with sofosbuvir and ribavirin (n = 207) compared to placebo (n = 71) in subjects who are interferon intolerant, ineligible or unwilling. Subjects were randomised in 3:1 ratio and stratified by cirrhosis (presence versus absence).

Treated subjects (n = 278) had a median age of 54 years (range: 21 to 75); 54% of the subjects were male; 91% were White; 5% were Black; 11% were Hispanic or Latino; mean body mass index was 28 kg/m2 (range: 18 to 53 kg/m2); 70% had baseline HCV RNA levels greater than 6 log10 IU/mL; 16% had cirrhosis; 49% had HCV genotype 3. The proportions of subjects who were interferon intolerant, ineligible, or unwilling were 9%, 44%, and 47%, respectively. Most subjects had no prior HCV treatment (81.3%). Table 9 presents the response rates for the treatment groups of sofosbuvir + ribavirin and placebo.

Table 9: Response rates in study POSITRON

  SOF+RBV

12 weeks

(n = 207)
 Placebo

12 weeks

(n = 71)
 
Overall SVR12
 78% (161/207)
 0/71
 
Genotype 2
 93% (101/109)
 0/34
 
Genotype 3
 61% (60/98)
 0/37
 
Outcome for subjects without SVR12
    
On-treatment virologic failure
 0/207
 97% (69/71)
 
Relapsea
 20% (42/205)
 0/0
 
Otherb
 2% (4/207)
 3% (2/71)

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).

The SVR12 rate in the sofosbuvir + ribavirin treatment group was statistically significant when compared to placebo (p <0.001).

Table 10 presents the subgroup analysis by genotype for cirrhosis and interferon classification.

Table 10: SVR12 rates for selected subgroups by genotype in POSITRON

  SOF+RBV

12 weeks
 
Genotype 2

(n = 109)
 Genotype 3

(n = 98)
 
Cirrhosis
    
No
 92% (85/92)
 68% (57/84)
 
Yes
 94% (16/17)
 21% (3/14)
 
Interferon classification
    
Ineligible
 88% (36/41)
 70% (33/47)
 
Intolerant
 100% (9/9)
 50% (4/8)
 
Unwilling
 95% (56/59)
 53% (23/43)
 
Previously treated adults - FUSION (study 108)

FUSION was a randomised, double-blinded study that eva luated 12 or 16 weeks of treatment with sofosbuvir and ribavirin in subjects who did not achieve SVR with prior interferon-based tre