1. SOF/VEL ± RBV in genotype 3 with compensated cirrhosis
Randomisation *
1:1
Open label
Design
W12
HCV genotype 3
Treatment-naïve or treatment-experienced (including NS3/4 or NS5B inhibitors)
Compensated cirrhosis (defined by biopsy or Fibroscan > 12.5 kPa or the combination of Fibrotest > 0.75 AND APRI > 2)
Patients with HIV co-infection eligible
N = 101
SOF/VEL
SVR12
SOF/VEL + RBV
N = 103
* Stratification by treatment experience
SOF/VEL: 400/100 mg 1 tablet QD
Patients enrolled in 29 sites in Spain
Primary endpoint
SVR12 (HCV < 15 IU/mL)
SOF/VEL + RBV G3 cirrhosis
Esteban R. Gastroenterology. 2018;155:1120-7 1

2. SOF/VEL ± RBV in genotype 3 with compensated cirrhosis
Baseline characteristics
SOF/VEL
12W
N = 101
SOF/VEL + RBV 12W
N = 103
Median age, years (range)
51 (31-70)
51 (31-85)
Male, N (%)
75 (74)
87 (85)
Race: White, N (%)
84 (83)
95 (92)
Median BMI, kg/m2 (range)
27 (18-40)
27 (18-47)
HIV co-infection, N (%)
16 (16)
14 (14)
Median HCV RNA, log10 IU/mL (range)
6.2 (4-7.5)
6.3 ( )
Treatment-experienced, N (%)
27 (27)
28 (27)
SOF/VEL + RBV G3 cirrhosis
SOF/VEL + RBV G3 cirrhosis
Esteban R. Gastroenterology. 2018;155:1120-7 2

3. SOF/VEL ± RBV in genotype 3 with compensated cirrhosis
Primary Endpoint (SVR12)
101
103 91 96 %
N =
Relapse 5 2
Non-responder 1
Lost to follow-up
2 ( 1 for AE)
Discontinuation due to AE
NS5A RAS: 19% in SOF/VEL (SVR12: 84%), 22% in SOF/VEL + RBV (SVR12: 96%)
Patients with Y93H: N = 4 in SOF/VEL (SVR12: 50%), N = 9 in SOF/VEL + RBV (SVR12: 88.9%)
SOF/VEL + RBV G3 cirrhosis
SOF/VEL + RBV G3 cirrhosis
Esteban R. Gastroenterology. 2018;155:1120-7 3

4. SOF/VEL ± RBV in genotype 3 with compensated cirrhosis
Primary Endpoint (SVR12) by prior treatment 28 27 75 74
Treatment naive (N = 149)
Treatment experienced (N = 55) 89 96 %
N =
Relapse 4 1
Non-responder
Lost to follow-up 2
Discontinuation due to AE
SOF/VEL + RBV G3 cirrhosis
SOF/VEL + RBV G3 cirrhosis
Esteban R. Gastroenterology. 2018;155:1120-7 4

5. SOF/VEL ± RBV in genotype 3 with compensated cirrhosis
Adverse events (AE) and laboratory abnormalities, N (%)
SOF/VEL
12W
N = 101
SOF/VEL + RBV 12W
N = 103
Any AE / grade 3-4 AE
48 (48%) / 2 (2%)
77 (75%) / 1 (1%)
Serious AE (all unrelated to treatment)
4 (4%)
2 (2%)
AE leading to discontinuation of SOF/VEL
1 (1%)
AE leading to discontinuation of RBV -
AE > 10% in either group
Asthenia
Headache
Insomnia
12 (12%)
8 (8%)
28 (27%)
25 (24%)
Laboratory abnormalities
Grade 3-4
Hemoglobin < 10 g/dL
Hemoglobin < 8.5 g/dL
7 (7%)
16 (16%)
5 (5%)
SOF/VEL + RBV G3 cirrhosis
SOF/VEL + RBV G3 cirrhosis
Esteban R. Gastroenterology. 2018;155:1120-7 5

6. SOF/VEL ± RBV in genotype 3 with compensated cirrhosis
Conclusion
High rates of SVR12 were observed with 12 weeks of SOF/VEL ± RBV in patients with GT3 and compensated cirrhosis
Adding RBV reduced the relapse rate from 5% to 2%
Treatment was well-tolerated
SOF/VEL + RBV G3 cirrhosis
SOF/VEL + RBV G3 cirrhosis
Esteban R. Gastroenterology. 2018;155:1120-7 6