(VALENCE)
 SOF+RBV 24 weeks
 Overall
 93% (98/105)
 
No cirrhosis
 94% (86/92)
 
Cirrhosis
 92% (12/13)
 
Treatment-experienced

(VALENCE)
 SOF+RBV 24 weeks
 Overall
 77% (112/145)
 
No cirrhosis
 85% (85/100)
 
Cirrhosis
 60% (27/45)
 
Treatment-naïve co-infected with HIV

(PHOTON-1)
 SOF+RBV 12 weeks
 Overall
 67% (28/42)
 
No cirrhosis
 67% (24/36)
 
Cirrhosis
 67% (4/6)
 
Treatment-experienced co-infected with HIV

(PHOTON-1)
 SOF+RBV 24 weeks
 Overalla
 92% (12/13)
 
No cirrhosisa
 100% (8/8)
 
Cirrhosisa
 80% (4/5)
 
Treatment-naïve

(ELECTRONb and PROTONb)
 SOF+PEG+RBV 12 weeks
 Overallc
 97% (38/39)
 
Treatment-experienced

(LONESTAR-2b)
 SOF+PEG+RBV 12 weeks
 Overall
 83% (20/24)
 
No cirrhosis
 83% (10/12)
 
Cirrhosis
 83% (10/12)

n = number of subjects with SVR12 response; N = total number of subjects per group.

a. These data are preliminary.

b. These are exploratory or Phase 2 studies. The outcomes should be interpreted with caution, as subject numbers are small and SVR rates may be impacted by the selection of patients. In the ELECTRON study (N = 11), the duration of peginterferon alfa ranged from 4-12 weeks in combination with sofosbuvir + ribavirin.

c. All patients were non-cirrhotic in these two studies.

Table 21: Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 4, 5 and 6 HCV infection

Patient population

(Study number/name)
 Regimen/Duration
 Subgroup
 SVR12 rate % (n/N)
 
Treatment-naïve

(NEUTRINO)
 SOF+PEG+RBV 12 weeks
 Overall
 97% (34/35)
 
No cirrhosis
 100% (33/33)
 
Cirrhosis
 50% (1/2)
 
n = number of subjects with SVR12 response; N = total number of subjects per group.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with sofosbuvir in one or more subsets of the paediatric populations in the treatment of chronic hepatitis C (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties
 Sofosbuvir is a nucleotide prodrug that is extensively metabolised. The active metabolite is not observed. The predominant (>90%) metabolite, GS-331007, is inactive. It is formed through sequential and parallel pathways to the formation of active metabolite.

Absorption

The pharmacokinetic properties of sofosbuvir and the predominant circulating metabolite GS-331007 have been eva luated in healthy adult subjects and in subjects with chronic hepatitis C. Following oral administration, sofosbuvir was absorbed quickly and the peak plasma concentration was observed ~0.5-2 hour post-dose, regardless of dose level. Peak plasma concentration of GS-331007 was observed between 2 to 4 hours post-dose. Based on population pharmacokinetic analysi