Hepatitisweb study

Hepatitisweb study

Sofosbuvir in Genotype 2 or 3 FUSION Trial

Phase 3

*Note: Published in NEJM in tandem with POSITRON Trial (GT 2,3 Unable to receive PEG)

Treatment Experienced

Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

Hepatitisweb studySource: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Features

FUSION Trial: Features

Design: Randomized, controlled, blinded phase 3 trial comparing 12 and 16 weeks of sofosbuvir + ribavirin in treatment-experienced HCV GT 2 or 3

Setting: 67 sites in US, Canada, New Zealand, enrolled May-July 2012

Entry Criteria - Treatment-experienced (failed prior interferon-based therapy) - HCV RNA ≥ 10,000 IU/ml

Patient Characteristics- N = 201 HCV-monoinfected patients- HCV genotype: 2 (34%); 3 (63%) - IL28B genotype: 70% non-CC- Prior treatment failure: 75% relapse; 25% nonresponse - Age and sex: mean age 54 (range 24-70); 70% male- Race: 87% white; 3% black- Liver disease: 34% had cirrhosis

Primary End-Point: SVR12

Hepatitisweb studySource: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

N =98 Sofosbuvir + RBV16 weeks

Sofosbuvir + RBV12 weeks

N =103

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Design

Placebo

Drug DosingSofosbuvir: 400 mg once dailyWeight-Based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg

0 24Week 12 16 28

SVR12

SVR12

Hepatitisweb study

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Results

FUSION: HCV RNA <25 IU/ml by Study Timepoint

Source: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

Week 4 End of Tx SVR120

20

40

60

80

10097 100

50

98 100

73

SOF + RBV (12 wk) SOF + RBV (16 wk)

Pa

tie

nts

(%

) w

ith

HC

V R

NA

< 2

5 IU

/ml

SOF= Sofosbuvir; RBV = Ribavirin

97/100 93/95 100/100 95/95 50/100 69/95

Hepatitisweb study

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Results

FUSION: SVR12 by Genotype and Treatment Duration

Source: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

GT 2 _x000d_(n=68) GT 3 _x000d_(n=127)0

20

40

60

80

100

86

30

94

62

SOF + RBV (12 wks) SOF + RBV (16 wks)

Pat

ien

ts (

%)

wit

h S

VR

12

SOF = Sofosbuvir; RBV = Ribavirin

31/36 30/32 19/64 39/63

Hepatitisweb study

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Results

FUSION: SVR12 by Liver Disease

Source: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

No Cirrhosis_x000d_(n=127) Cirrhosis_x000d_(n=68)0

20

40

60

80

100

61

31

76

66

SOF + RBV (12 wks) SOF + RBV (16 wks)

Pat

ien

ts (

%)

wit

h S

VR

12

SOF = Sofosbuvir; RBV = Ribavirin

39/64 48/63 11/36 21/32

Hepatitisweb study

No Cirrhosis Cirrhosis0

20

40

60

80

100

37

19

63 61

SOF + RBV (12 wks) SOF + RBV (16 wks)

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Results

FUSION: SVR12 by Genotype, Cirrhosis, and Duration of Therapy

Source: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

No Cirrhosis Cirrhosis 0

20

40

60

80

100

96

60

100

78

SOF + RBV (12 wks) SOF + RBV (16 wks)

SOF = Sofosbuvir; RBV = Ribavirin

Genotype 2 Genotype 3

25/26 23/23 6/10 7/9 14/38 25/40 5/26 14/23

Hepatitisweb studySource: Jacobson I, et al. N Engl J Med. 2013;368:1867-77.

Sofosbuvir + RBV in Treatment-Experienced HCV GT 2 or 3FUSION Trial: Conclusions

Conclusions: “Our findings suggest that 12 weeks of treatment with

sofosbuvir and ribavirin can be an effective option for patients with HCV

genotype 2 infection. However, for patients with genotype 3 infection,

particularly those who have cirrhosis or who have not had a response to

prior treatment with interferon, extending the duration of treatment

to 16 weeks may provide an additional benefit.”

*Note: This conclusion pertains to both the FUSION and POSITRON trials, which were published in tandem

Hepatitisweb study

Hepatitisweb study

This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects.

Hepatitis C Online

www.hepatitisc.uw.edu

Hepatitis Web Study

http://depts.washington.edu/hepstudy/

Funded by a grant from the Centers for Disease Control and Prevention.