1. Genotype 1 HCV in 2016: Clinical Decision Making in a Time of Plenty
Ira M. Jacobson, MD Chair, Department of Medicine Mount Sinai Beth Israel Senior Faculty and Vice-Chair, Department of Medicine Icahn School of Medicine at Mount Sinai New York, New York
Supported by educational grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck, and ViiV Healthcare.

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3. Disclosures
Ira. M. Jacobson, MD, has disclosed that he has received funds for research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, and Merck; has served on speaker bureaus for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Janssen; and has received consulting fees from AbbVie, Bristol- Myers Squibb, Gilead Sciences, Intercept, Janssen, Merck, and Trek.

4. New Regimens and Data for Genotype 1 HCV Infection
AASLD Guidance
Updated July 6, 2016
AASLD guidance stratifies regimens as “recommended” and “alternative”
AASLD, American Association for the Study of Liver Diseases; HCV, hepatitis C virus.
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

5. AASLD: Recommended and Alternative Regimens for GT1 Without Cirrhosis
Nucleotide
No nucleotide
Population
LDV/SOF
DCV + SOF
SMV + SOF
SOF/VEL
GZR/EBR
OBV/PTV/RTV + DSV
GT1a
12 wks
16 wks + RBV†
12 wks + RBV
GT1b
AASLD, American Association for the Study of Liver Diseases; DCV, daclatasvir; DSV, dasabuvir; EBR, elbasvir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; OBV, ombitasvir; PTV, paritaprevir; RAV, resistance associated variant; RBV, ribavirin; RTV, ritonavir; SMV, simeprevir; SOF, sofosbuvir; VEL, velpatasvir.
†If NS5A RAVs present.
Recommended Alternative
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. July 2016.

6. AASLD: Recommended and Alternative Regimens for GT1 With Compensated Cirrhosis
Nucleotide
No nucleotide
Population
LDV/SOF
DCV + SOF
SMV + SOF
SOF/VEL
GZR/EBR
OBV/PTV/RTV + DSV
GT1a
Naive
PR exp
12 wks
12 wks + RBV
or 24 wks
24 wks ± RBV
24 wks ±
RBV*
16 wks + RBV† 12 wks
16 wks + RBV†
24 wks + RBV
GT1b
+ RBV
RBV
AASLD, American Association for the Study of Liver Diseases; DCV, daclatasvir; DSV, dasabuvir; EBR, elbasvir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; OBV, ombitasvir; PR, peginterferon/ribavirin; PTV, paritaprevir; RAV, resistance associated variant; RBV, ribavirin; RTV, ritonavir; SMV, simeprevir; SOF, sofosbuvir; VEL, velpatasvir.
*Not with Q80K.
†If NS5A RAVs present.
Recommended Alternative
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. July 2016.

7. Sofosbuvir/Velpatasvir: Approved June 2016
Genotype 1a or 1b, without cirrhosis or with compensated cirrhosis (Child-Pugh A), treatment naive or treatment experienced
12 weeks sofosbuvir/velpatasvir
Genotype 1a or 1b, with decompensated cirrhosis (Child-Pugh B or C), treatment naive or treatment experienced
12 weeks sofosbuvir/velpatasvir + ribavirin
Slide credit: clinicaloptions.com
Sofosbuvir/velpatasvir prescribing information.

8. ASTRAL-1: VEL/SOF FDC for 12 Wks in GT1/2/4/5/6 With and Without Cirrhosis
Velpatasvir (GS-5816): pangenotypic HCV NS5A inhibitor
GT3 pts evaluated in separate study
19% cirrhosis, 32% treatment experienced 99 99
100 98 75
SVR12* (%)
FDC, fixed-dose combination; GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir; VEL, velpatasvir. 50 25
n/N =
618/624
206/210
117/118
Overall
GT1a
GT1b
*HCV RNA < 15 IU/mL
Slide credit: clinicaloptions.com
Feld JJ, et al. AASLD Abstract LB-2.

9. ASTRAL-4: VEL/SOF FDC for HCV in Pts With Decompensated Liver Disease
Treatment-naive or treatment-experienced pts with GT1-6 HCV infection and CTP B cirrhosis (N = 267)
55% treatment experienced; 95% MELD < 15; 75% to 83% ascites; 58% to 66% encephalopathy
GT1: 78%; GT3: 15%, GT2/4/6: 8%
Wk 0
Wk 12
Wk 24
Wk 36
SVR12
VEL/SOF*
n = 90
CTP, Child-Turcotte-Pugh; FDC, fixed-dose combination; GT, genotype; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
SVR12
n = 87
VEL/SOF* + RBV
SVR12
n = 90
VEL/SOF*
*100 mg/400mg
Slide credit: clinicaloptions.com
Charlton MR, et al. AASLD Abstract LB-13.

10. ASTRAL-4: VEL/SOF FDC for HCV in Pts With Decompensated Liver Disease
SOF/VEL 12 wks SOF/VEL + RBV 12 wks SOF/VEL 24 wks 94 96
100 92 86 88 83 80 60
SVR12 (%) 40 20
n/N =
75/90
82/87
77/90
60/68
65/68
65/71
Overall
Genotype 1
Breakthrough, n
Relapse, n
LTFU, n
Death, n - 11 1 3 1 2 - 1 7 3 2 - 5 1 2 - 1 2 - 3
AE, adverse event; D/c, discontinued; FDC, fixed-dose combination; HA, headache; Hb, hemoglobin; HCV, hepatitis C virus; LTFU, lost to follow-up; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
D/c due to AE: 3% (n = 9)
Death due to AE: 3% (n = 9)
Fatigue (29%); nausea (23%); HA (22%); anemia (13%; 31% in RBV arm)
AE more frequent with RBV
RBV arm: Hb < 10 mg/dL, 23%; Hb < 8.5 mg/dL, 7%
RBV decreased in 37% and d/c in 17%
Slide credit: clinicaloptions.com
Charlton MR, et al. AASLD Abstract LB-13

11. ASTRAL-5: VEL/SOF FDC for 12 Wks in Pts Coinfected With HCV and HIV-1
SVR12
N = 106
VEL/SOF Wk 12 24
100
100
100 95 95 92 92 80
2 relapse
1 LTFU
1 withdrew consent 60
1 LTFU
SVR12 (%)
FDC, fixed-dose combination; GT, genotype; HCV, hepatitis C virus; LTFU, lost to follow-up; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. 40 20
99/ 104
62/ 65
11/ 12
11/ 11
11/ 12
4/ 4
n/N =
Total
GT1a
GT1b
GT2
GT3
GT4
Slide credit: clinicaloptions.com
Wyles D, et al. EASL Abstract PS104.

12. Grazoprevir/Elbasvir: Approved Jan 2016
Genotype 1a, with/without compensated cirrhosis, treatment naive or treatment experienced
Without NS5A RAVs: GZR/EBR, 12 wks
With NS5A RAVs: GZR/EBR + RBV, 16 wks*
RAVs at positions 28, 30, 31, 93
Genotype 1b, with/without compensated cirrhosis, treatment naive or treatment experienced
GZR/EBR, 12 wks
RAV testing not indicated
EBR, elbasvir; GZR, grazoprevir; RAV, resistance associated variant.
*Listed as “alternative” regimen.
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

13. C-EDGE TN: 12 Wks of GZR/EBR in Genotype 1, 4, or 6
100
100 95 97 99 94 92 80 80 60
SVR12 (%) 40
299/
316
231/
246
68/ 70
144/
157
129/
131
18/ 18 8/ 10 20
n/N =
All Pts
Noncirrhotics
Cirrhotics
GT1a
GT1b 3 1 9
GT4 1
GT6 2
Non-VF
Breakthrough
Relapse
Good safety and tolerability profile
No drug-related serious AEs; 2 deaths unrelated to drug
No concurrent ALT/bilirubin increase
Lower SVR12 rates in pts with BL NS5A RAVs (2/9, 22%); associated with > 5-fold loss of EBR susceptibility
Virologic failure only if baseline HCV RNA > 800,000 IU/mL
AE, adverse event; ALT, alanine aminotransferase; BL, baseline; EBR, elbasvir; GT, genotype; GZR, grazoprevir; RAV, resistance associated variant; SVR, sustained virologic response; VF, virologic failure.
Slide credit: clinicaloptions.com
Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

14. C-EDGE TE: 12 or 16 Wks of GZR/EBR ± RBV in Treatment-Experienced GT1, 4, or 692 94 97
100 80 60 40 20 92
12 wks
SVR12 (%, 95% CI)
16 wks
97/
105
98/
104
97/
105
103/
106
n/N =
No RBV
+ RBV
No RBV
+ RBV
Breakthrough
Rebound
Relapse
LTFU/early d/c 6 2
0060
1241
0003
*ITT population.
AASLD, American Association for the Study of Liver Diseases; d/c, discontinued; EBR, elbasvir; GT, genotype; GZR, grazoprevir; ITT, intent to treat; LTFU, lost to follow-up; RAV, resistance associated variant; RBV, ribavirin; SVR, sustained virologic response.
Virologic failures driven by RAVs
Analysis from AASLD 2015 shows that presence of baseline NS5A RAVs by population sequencing or next-generation sequencing (with 10% to 20% cutoff) is predictive of failure
Kwo P, et al. EASL Abstract P0886. Jacobson I, et al. AASLD Abstract LB22.
Slide credit: clinicaloptions.com

15. C-EDGE TE: Efficacy of 12 Wks of GZR/EBR ± RBV by Baseline RAVs
SVR12, n/N (%)
Total
NS3 Variants Not Detectable
NS3 RAVs
≤ 5-Fold Shift
> 5-Fold Shift
GT1a
95%
107/112 (96)
104/111 (94)
GT1b
99%
133/135 (99)
9/9 (100)
1/1 (100%)
NS5A Variants Not Detectable
NS5A RAVs
190/192 (99)
10/10 (100)
11/21 (52)
127/127 (100)
16/18 (89)
EBR, elbasvir; GT, genotype; GZR, grazoprevir; RAV, resistance associated variant; RBV, ribavirin; SVR, sustained virologic response.
Should baseline RAV testing be done with this regimen?
The NS5A RAVs that matter are in the 28, 30, 31, and 93 positions
Slide credit: clinicaloptions.com
Kwo P, et al. EASL Abstract P0886.

16. C-SURFER: Grazoprevir/Elbasvir in Pts With GT1 HCV and Stage 4/5 CKD
Treatment Wk 12
Follow-up Wk 4
Follow-up Wk 16
SVR12*
Randomized period
GT1 HCV–infected pts with stage 4/5 CKD (n = 224)
Grazoprevir/Elbasvir (n = 111)
99%
Open-label period
Placebo (n = 113)
Grazoprevir/Elbasvir (n = 113)
98%
Grazoprevir/elbasvir dosed orally 100 mg/50 mg once daily. This study also included a pharmacokinetic analysis (n = 11) in which pts were treated as in the randomized grazoprevir/elbasvir study group.
76% on dialysis
34% with diabetes
52% GT1a, 48% GT1b
6% cirrhosis
*Modified full analysis set population.
CKD, chronic kidney disease; GT, genotype; HCV, hepatitis C virus; SVR, sustained virologic response.
Roth D, et al. Lancet. 2015;386:
Roth D, et al. Kidney Week Abstract SA-PO1100.
Slide credit: clinicaloptions.com

17. Daclatasvir + Sofosbuvir
Genotype 1a or 1b, treatment naive or experienced, without cirrhosis
DCV + SOF, 12 wks
Genotype 1a or 1b, treatment naive or experienced, with compensated cirrhosis
DCV + SOF ± RBV, 24 wks*
*Listed as “alternative” regimen
DCV, daclatasvir; RBV, ribavirin; SOF, sofosbuvir.
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

18. DCV + SOF ± RBV for 24 Wks in GT1 Pts With Advanced Liver Disease
SVR12 by Genotype
100
100 98 98 98 97 97 96 96 92 91 89 90 80 60
SVR12 (%) 40 20
GT, genotype; DCV, daclatasvir; mITT, modified intent to treat; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response.
All GT1
GT1a
GT1b
As observed
DCV + SOF
DCV + SOF + RBV
mITT
DCV + SOF
DCV + SOF + RBV
Slide credit: clinicaloptions.com
Welzel T, et al. EASL Abstract SAT-275.

19. Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir
Genotype 1a, treatment naive or experienced
No cirrhosis: OBV/PTV/RTV + DSV + RBV, 12 wks
With compensated cirrhosis: OBV/PTV/RTV + DSV + RBV, 24wks*
RAV testing not indicated
Genotype 1b, with/without compensated cirrhosis, treatment naive or experienced
OBV/PTV/RTV + DSV, 12 wks
DSV, dasabuvir; OBV, ombitasvir; PTV, paritaprevir; RAV, resistance associated variant; RBV, ribavirin; RTV, ritonavir.
*Listed as “alternative” regimen.
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

20. TURQUOISE III: 12 Wks of OBV/PTV/RTV + DSV Without RBV in Cirrhotic GT1b Pts
Virologic Response
100
100
100
100
100 80 60
Pts (%) 40 20
n/N =
60/60
60/60
60/60
60/60
RVR
EOTR
SVR4
SVR12
AASLD, American Association for the Study of Liver Diseases; DSV, dasabuvir; EOTR, end of treatment viral response; GT, genotype; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; RVR, rapid viral response; SVR, sustained virologic response.
AASLD guidance now recommends OBV/PTV/RTV + DSV 12 wks without RBV for GT1b cirrhotics
Still need 24 wks + RBV for GT1a cirrhotics, naive or experienced
Poordad F, et al. AASLD Abstract AASLD/IDSA. HCV Guidance. April 2016.
Slide credit: clinicaloptions.com

21. Real-World Efficacy of OBV/PTV/RTV ± DSV ± RBV: German HCV Registry Cohort
Efficacy population (complete follow-up): n = 543; safety population (initiated treatment): n = 1017
GT1: 88%; GT4: 12%; cirrhosis: 22% (CTP B/C: 7%); tx experienced: 59%
100 97 96 97 95 93 96
100 96 98 96
100 80
*Includes 13 pts with mixed or unknown GT1 subgenotype infection, all of whom achieved SVR. 60
SVR24 (%) 40 20
BOC, boceprevir; CTP, Child-Turcotte-Pugh; DSV, dasabuvir; GT, genotype; HCV, hepatitis C virus; IFN, interferon; OBV, ombitasvir; pegIFN, peginterferon; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; SVR, sustained virologic response; TVR, telaprevir; tx, treatment.
365/378
108/113
246/
254
51/ 51
121/
127
26/ 28
93/ 97 2/ 2
200/208
268/
274
46/ 48
n/N =
GT1 Total*
GT1 Total*
(peg)IFN ± RBV
GT1a
GT1b
GT4
GT1a
GT1b
GT4
Naive
TVR/BOC + pegIFN + RBV
Without Cirrhosis
With Cirrhosis
Slide credit: clinicaloptions.com
Hinrichsen H, et al. EASL Abstract GS07.

22. Real-World Efficacy of OBV/PTV/RTV ± DSV ± RBV: Israeli Cohort
Efficacy population (complete follow-up): n = 432; safety population (initiated treatment): n = 661
GT1: 100%; cirrhosis: 62% (CTP A/B: 98.5%/1.5%); tx exp’d: 62%
Post LT: n = 22
SVR12 mITT/overall: 82%/86%; 4 discontinued due to serious AEs, one of which achieved SVR 99 99
100 80
No cirrhosis
Cirrhosis
Pts With Undetectable
HCV RNA (%) 60 40
AE, adverse event; CTP, Child-Turcotte-Pugh; DSV, dasabuvir; GT, genotype; LT, liver transplantation; mITT, modified intent to treat; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; SVR, sustained virologic response; tx, treatment. 20
161/ 163
251/
253
*Excludes pts who did not achieve SVR12 for reasons other than virologic failure.
161/
163
251/
253
n/N =
SVR12 (mITT*)
Slide credit: clinicaloptions.com
Zuckerman E, et al. EASL Abstract PS004.

23. Real-World Safety of OBV/PTV/RTV ± DSV ± RBV: German and Israeli Cohorts
Most common AEs across both cohorts[1,2]: fatigue, pruritus, headache, insomnia, nausea, diarrhea (Israeli), anemia (German)
Serious AE: 2.1% to 3.8%
D/c for AE: 1.5% to 3.0%
3 deaths deemed unrelated to HCV therapy: stroke, MI, multiple organ failure
In Israeli cohort, 20 pts discontinued for AEs[2]
Serious AE: n = 12
Decompensation: n = 8
In Israeli cohort, several factors identified as significant predictors of hepatic decompensation[2]
Factor
P Value
Age older than 75 yrs
.005
Platelets < 90,000/mL
.03
Albumin < 3.5 g/dL
.048
CTP score ≥ 7
.07
MELD score > 10
.01
Previous decompensation
< .001
AE, adverse event; CTP, Child-Turcotte-Pugh; D/c, discontinued; DSV, dasabuvir; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; MI, myocardial infarction; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir.
1. Hinrichsen H, et al. EASL Abstract GS07.
2. Zuckerman E, et al. EASL Abstract PS004.
Slide credit: clinicaloptions.com

24. Ledipasvir/Sofosbuvir for GT1 Tx-Naive Noncirrhotics With HCV RNA < 6 M IU/mL:
Are 8 wks sufficient? Or are 12 wks better?
Established by retrospective analysis of ION-3
Many clinicians were initially uncomfortable
What do “real-world” data show?
GT, genotype; Tx, treatment.
Slide credit: clinicaloptions.com

25. 8 vs 12 Wks of LDV/SOF in Pts With GT1 HCV: HCV-TARGET and TRIO Network
Treatment-naive, noncirrhotic pts with GT1 HCV
HCV RNA < 6 M IU/mL in HCV-TARGET
HCV-TARGET[1]
TRIO Network[2] 97 97
100
100 95 96 80 80 60 60
SVR12 (%)
SVR12 (%) 40 40
GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; SOF, sofosbuvir; SVR, sustained virologic response. 20 20
n/N =
127/131
187/192
251/263
604/632
8 Wks
8 Wks
8 Wks
12 Wks
1. Terrault N, et al. AASLD Abstract Curry M, et al. AASLD Abstract 1046.
Slide credit: clinicaloptions.com

26. 8 Wks of LDV/SOF in Pts With GT1 HCV: German Real-World Single-Center Study
Pts noncirrhotic (100%) and primarily treatment naive (97%), GT1 (98%), and HCV RNA < 6 M IU/mL (96%) 99
100 80 60
SVR12 (%) 40
GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; SOF, sofosbuvir; SVR, sustained virologic response. 20
n/N =
127/128
8 Wks
Slide credit: clinicaloptions.com
Buggisch P et al, EASL Abstract SAT-242.

27. LDV/SOF: SVR12 by Treatment Regimen and Duration in Pts Without Cirrhosis
Pooled data from multiple trials, HCV RNA < 6 M IU/mL in 8-wk arm
With RAVs
No RAVs 98 99 99 99
100 80 60
SVR12 (%) 40
LDV, ledipasvir; RAV, resistance associated variant; SOF, sofosbuvir; SVR, sustained virologic response. 20
n/N =
30/32
107/108
187/189
504/509
8 Wks
12 Wks
Slide credit: clinicaloptions.com
Zeuzem S, et al. AASLD Abstract 91.

28. PPIs and Ledipasvir: Does Acid Suppression Matter?
PPI, proton pump inhibitor.

29. HCV-TARGET: Effect of PPI Use?
Pts treated according to local standards of care at 44 academic/ 17 community medical centers in North America/Europe
Virologic outcome known for 1074 pts
SVR12 According to Baseline PPI Use
PPI: No
PPI: Yes 98 98
100 80 60 40 20 93 93
SVR12 (%)
LDV, ledipasvir; PPI, proton pump inhibitor; SOF, sofosbuvir; SVR, sustained virologic response.
122/
124
28/ 30
456/
464
151/
163
n/N =
8-Wk LDV/SOF
12-Wk LDV/SOF
Slide credit: clinicaloptions.com
Terrault N, et al. AASLD Abstract 94.

30. TRIO Network: No Effect of PPI Use?
Real-world data from 2034 pts with GT1 HCV receiving LDV/SOF
A per protocol analysis (n = 1979) showed no effect of PPIs on SVR
SVR12 According to Baseline PPI Use 98
100 98 97 99
100 80 60 40 20 97
PPI: No
PPI: Yes
GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; PPI, proton pump inhibitor; SOF, sofosbuvir; SVR, sustained virologic response.
SVR12 (%)
230/234
41/ 41
1024/1045
287/297
243/246
113/116
n/N =
12 Wks
24 Wks
8 Wks
Slide credit: clinicaloptions.com
Afdhal N, et al. EASL Abstract LBP519.

31. TRIO Network: Predictors of Response to LDV/SOF by PPI Usage
Per protocol analysis (n = 1979)
n = 454
97%
PPI drug
Dexlansoprazole (n = 10)
Esomeprazole (n = 48)
Lansoprazole (n = 26)
P = .799
Omeprazole (n = 288)
“Caution with use of high dose PPIs with LDV/SOF”
Pantoprazole (n = 77)
Rabeprazole (n = 5)
PPI dose
Low (n = 282)
P = .965
High (n = 172)
LDV, ledipasvir; PPI, proton pump inhibitor; SOF, sofosbuvir.
PPI frequency
Once daily (n = 420)
P = .030
Twice daily (n = 34)
80%
90%
100%
Slide credit: clinicaloptions.com
Afdhal N, et al. EASL Abstract LBP519.

32. New Regimens

33. VEL/SOF + GS-9857 for 6 or 8 Wks in Treatment-Naive Pts With GT1-6 HCV
Genotype 1
Genotypes 1-6
No Cirrhosis
Cirrhosis 96
100 94
100
100 81 79 71 80 80 60 60
SVR (%)
SVR (%) 40 40 20 20
n/N =
53/67
95/99
25/35
36/36
31/33
25/31
No RBV 6 Wks
No RBV
8 Wks
No RBV 6 Wks
No RBV 8 Wks
No RBV 8 Wks
RBV 8 Wks
8 wks of VEL/SOF + GS9857 highly effective including pts with RAVs and cirrhosis
Single tablet QD in phase III
6 wks had high relapse
No benefit of RBV with 8 wks
Will the triplet be used as primary first-line treatment or as salvage treatment for persons who fail current DAAs?
DAA, direct-acting antiviral; GT, genotype; HCV, hepatitis C virus; QD, once daily; RAV, resistance associated variant; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
Slide credit: clinicaloptions.com
Gane EJ, et al. EASL Abstract SAT-138.

34. VEL/SOF + GS-9857 for 12 Wks in Treatment-Experienced GT1-6 HCV
BL Characteristics
(N = 128)
VEL/SOF + GS-9857
Cirrhosis, n (%)
61 (48)
Mean HCV RNA, log10 IU/mL (range)
6.3 ( )
HCV genotype, n (%) 1
63 (49) 2
21 (16) 3
35 (27)
4/6
9 (7)
DAA experience, n (%)
None (GT2-6 only)
27 (21)
1 DAA class
36 (28)
≥ 2 DAA classes
65 (51) 99
100
100 80 60
SVR12 (%) 40 20
n/N =
127/128
63/63
BL, baseline; DAA, direct-acting antiviral; GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
Overall
GT1
1 pt relapsed at posttreatment Wk 8
Slide credit: clinicaloptions.com
Lawitz E, et al. EASL Abstract PS008.

35. SURVEYOR-I/II: ABT-493 + ABT-530 for 8 or 12 Wks in Pts With GT1 or 2 HCV
Open-label, treatment naive or pegIFN/RBV experienced
SVR12 in Pts With GT1 HCV
8 wks 12 wks
100 97 96
100
100 80 80 60 60
SVR12 (%)
SVR12 (%) 40 40
GT, genotype; HCV, hepatitis C virus; ITT, intent to treat; mITT, modified intent to treat; pegIFN, peginterferon; RBV, ribavirin; SVR, sustained virologic response. 20 20
n/N =
33/34
33/33
26/27
ITT
mITT
Cirrhosis[2]
No Cirrhosis[1]
1. Poordad F, et al. EASL Abstract SAT Gane EJ, et al. EASL Abstract SAT-135.
Slide credit: clinicaloptions.com

36. C-CREST 1 and 2: MK-3682/GZR/MK-8408 for 8 Wks in Tx-Naive Noncirrhotic Pts
GT1, 2, or 3 without cirrhosis (N = 240)
In GT1 arm, no impact of baseline NS5A, NS3, or NS5B RAVs on SVR12
100
100 87 80 60 40
MK-3682 (300 mg) + GZR + MK-8408
MK-3682 (450 mg) + GZR + MK-8408 20
n/N =
24/24
20/23
GT, genotype; GZR, grazoprevir; RAV, resistance associated variant; SVR, sustained virologic response; Tx, treatment.
Genotype 1
Slide credit: clinicaloptions.com
Gane EJ, et al. EASL Abstract 139.

37. Conclusions 5 highly effective regimens approved for GT1 HCV
Newest is GZR/EBR, which requires RAV testing in GT1a
Need for extended therapy and/or RBV in cirrhotics depending on regimen, GT1 subtype, and prior treatment status
Real-world data reflect efficacy in clinical trials
Data support 8 wks of LDV/SOF in GT1 treatment-naive noncirrhotics with HCV RNA < 6 M IU/mL
High-dose PPIs should be avoided with LDV (same likely to be the case with VEL based on clinical trial designs)
GT, genotype; GZR, grazoprevir; HCV, hepatitis C virus; LDV, ledipasvir; PPI, proton pump inhibitor; RAV, resistance associated variant; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir.
Slide credit: clinicaloptions.com

38. New Regimens in Development
Promising regimens
Second-generation 2-drug regimen of ABT-493/ ABT-530
Triplet regimens of PI/NS5A/Nuc
New regimens may offer 8-week option for noncirrhotics
High SVR rates in DAA failures
DAA, direct-acting antiviral; Nuc, nucleotide analog; PI, protease inhibitor; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
Slide credit: clinicaloptions.com

39. Go Online for More CCO Coverage of HCV!
Multimedia modules featuring video of expert faculty discussions of challenging cases Downloadable slidesets for your own study or presentations
clinicaloptions.com/hcv