1. Non–Genotype 1 HCV Now and in the Near Future

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3. Faculty
Jordan J. Feld, MD, MPH Associate Professor of Medicine University of Toronto Hepatologist Toronto Centre for Liver Disease Sandra Rotman Centre for Global Health Toronto, Canada Andrew J. Muir, MD Chief, Division of Gastroenterology Associate Professor of Medicine Department of Medicine Director, Gastroenterology/Hepatology Research Duke Clinical Research Institute Duke University School of Medicine Durham, North Carolina

4. Disclosures
Jordan J. Feld, MD, MPH, has disclosed that he has received consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, and Merck and funds for research support from Abbott, AbbVie, Gilead Sciences, Janssen, and Merck. Andrew J. Muir, MD, has disclosed that he has received consulting fees from AbbVie, Achillion, Bristol- Myers Squibb, Gilead Sciences, Intercept, Janssen, Lumena, Merck, NGM Biopharm, Regulus Therapeutics, Salix, Shire, and Therevance and funds for research support from AbbVie, Achillion, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hologic, Intercept, Janssen, Merck, NGM Biopharma, and Roche.

5. Genotype 3 HCV
HCV, hepatitis C virus.

6. HCC-Free Survival by Genotype[2]
Genotype 3 Is Important
Second most common genotype globally[1]
10% to 15% of HCV cases in the US
Associated with more rapid progression of fibrosis and higher risk of HCC[2]
Suboptimal responses to first-generation DAAs
HCC-Free Survival by Genotype[2]
1.0
P = .001
0.8
Genotype 4
Genotype 2
0.6
HCC-Free Survival
Genotype 1
0.4
0.2
Genotype 3
DAA, direct-acting antiviral; HCC, hepatocellular carcinoma; HCV, hepatitis C virus. 2 4 6 8 10 12
Yrs
Genotype 1
Genotype 2
Genotype 3
Genotype 4
251 33 25 44
207 27 20 37
166 24 10 25 85 8 3 6 56 3 1
1. Messina JP, et al. Hepatology. 2015;61: Nkontchou G, et al. J Viral Hepat. 2011;18:e516-e522.
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7. GT3: SOF + RBV Far From Ideal
SOF + RBV for 24 wks for GT3 HCV
100 95
No cirrhosis 92 87
Cirrhosis 80 62 61
14/ 23
Trial,
16 wks 60 58
21/ 36
Real
World
SVR12 (%) 44
22/ 50
Real
World 40 20
87/ 92
12/ 13
85/ 98
29/ 47
GT, genotype; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response.
Trial
Trial
Naive
Experienced
Cirrhosis even more of a problem in the real world
Be careful about extrapolation of results…
Zeuzem S, et al. N Engl J Med. 2014;370: Feld JJ, et al. Clin Infect Dis ; submitted. Jacobson IM, et al. N Engl J Med. 2013;368:
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8. Can PegIFN Still Be Used?
BOSON: SOF + PegIFN/RBV vs SOF + RBV
SOF + RBV 16 wks
SOF + RBV 24 wks
SOF + pegIFN/RBV 12 wks 96 91 94
100 90 82 86 83 82 77 76 57 80 47 60
SVR12 (%) 40 20
PegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response.
58/ 70
65/ 72
68/ 71
12/ 21
18/ 22
21/ 23
41/ 54
44/ 54
49/ 52
17/ 36
26/ 34
30/ 35
n/N =
No Cirrhosis
Cirrhosis
No Cirrhosis
Cirrhosis
Treatment Experienced
Treatment Naive
Clear advantage to SOF + pegIFN/RBV, especially in cirrhosis
Only 1 SOF + pegIFN/RBV discontinuation—good safety
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Foster GR, et al. Gastroenterology. 2015;149:

9. But Using PegIFN Is Not Ideal . . . < 5% Uptake in HCV TARGET
PegIFN, peginterferon.
Slide credit: clinicaloptions.com
Feld JJ, et al. Clin Infect Dis. 2016;submitted.

10. What About SOF/LDV for GT3 HCV?
SOF/LDV + RBV for 12 wks, TE
SOF/LDV + RBV for 12 wks, TN 94
100
100 89 89 82 79 80 80 73 60 60
SVR12 (%)
SVR12 (%)
Relapse 3
LTFU 1
Death 0
Relapse 5
LTFU 2
Death 1 40 40
GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; TE, treatment experienced; TN, treatment naïve. 20
41/ 50
16/ 22 20
99/
111
66/ 70
31/ 39
25/ 28
n/N =
n/N =
Overall
F0-3
Cirrhosis
Overall
F0-3
Cirrhosis
LDV not active against GT3 HCV in vitro…
Better than expected but still not optimal in cirrhotics
Gane EJ, et al. AASLD Abstract LB-11. Feld J, et al. EASL Abstract SAT-183.
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11. Is SOF + DCV More Effective in GT3 HCV?
ALLY-3: SOF + DCV for 12 wks for GT3 HCV
Overall
Naive
Experienced 97
100 96
100
100 94 80 80 80 69 63 58 60 60 60
SVR12 (%) 40 40 40
DCV, daclatasvir; GT, genotype; HCV, hepatitis C virus; IFN, interferon; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response. 20 20 20
105/
109
20/ 32
73/ 75
11/ 19
32/ 34 9/ 13
n/N =
F0-3
Cirrhosis
F0-3
Cirrhosis
F0-3
Cirrhosis
Very good IFN/RBV-free regimen for GT3 noncirrhotics
Unfortunately, not the answer for cirrhosis—at least not for 12 wks
Slide credit: clinicaloptions.com
Nelson DR, et al. AASLD Abstract LB-3.

12. Leaves us without a clear answer…RBV helpful but duration unclear
Would Longer Help?
ALLY-3+: GT3 HCV pts with F3/F4 treated with SOF + DCV + RBV for 12 or 16 wks
All 4 relapses with Y93H
Key point!
100
100
100 89 88 86 83 80
12 wks
16 wks 60
SVR12 (%) 40
DCV, daclatasvir; GT, genotype; HCV, hepatitis C virus; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; TE, treatment experienced. 20
n/N =
6/6
8/8
15/17
16/18
14/16
12/14 F3
Cirrhosis
TE Cirrhosis
Leaves us without a clear answer…RBV helpful but duration unclear
Slide credit: clinicaloptions.com
Leroy V, et al. AASLD Abstract LB-3.

13. Lessons From the “Real World”
GT3 HCV pts treated with SOF + DCV ± RBV for 24 wks in European EAP
Pts with advanced liver disease (85% cirrhotic)
100 86 88 87
DCV + SOF
DCV + SOF + RBV
All pts 80 60
HCV RNA < LLOQ, TD or TND (% ± 95% CI) 40 20
42/ 49
29/ 33
71/ 82
AE, adverse event; DCV, daclatasvir; EAP, early access program; GT, genotype; HCV, hepatitis C virus; LLOQ, lower limit of quantification; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; TD, target detected; TND, target not detected.
n/N =
Not Achieving SVR12
Breakthrough
Relapse
Discontinuation (AE)
Death 7 1 3 4 3 1 11 1 6 3
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Welzel TM, et al. AASLD Abstract 37.

14. Effective but Still Not Ideal in Cirrhosis
Cirrhotic GT3 HCV pts treated with SOF + DCV ± RBV for 12 or 24 wks in French EAP
100
DCV + SOF
DCV + SOF + RBV
100 86 81 80 70 60
HCV RNA < LLOQ,TD/TND (%) 40 20
23/ 33 4/ 4
116/
135
39/ 48
n/N =
DCV, daclatasvir; EAP, early access program; GT, genotype; HCV, hepatitis C virus; LLOQ, lower limit of quantification; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; TD, target detected; TND, target not detected.
12 Wks
24 Wks
24 wks necessary
Unclear role of RBV
No real trial data…hard to interpret
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Hezode C, et al. AASLD Abstract 206.

15. Less Effective With Decompensation
GT3 HCV pts in French EAP treated with SOF + DCV ± RBV for 12 or 24 wks
100
Child-Pugh A Child-Pugh B or C 90 85 80 80 71 70 60
HCV RNA < LLOQ,TD/TND (%) 40 33 20
DCV, daclatasvir; EAP, early access program; GT, genotype; HCV, hepatitis C virus; LLOQ, lower limit of quantification; RBV, ribavirin; SOF, sofosbuvir; TD, target detected; TND, target not detected.
24/ 30 2/ 6
90/
100
12/ 17
28/ 33 7/ 10
n/N =
12 Wks
DCV + SOF ± RBV
24 Wks
DCV + SOF
24 Wks
DCV + SOF + RBV
SOF + DCV is not ideal therapy for pts with advanced cirrhosis
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Hezode C, et al. AASLD Abstract 206.

16. Summary of Current Therapy
SOF + RBV for 24 wks
Suboptimal SVR rates, particularly in pts with cirrhosis
SOF + PegIFN/RBV for 12 wks
Good option if you can convince pts to take it!
SOF + DCV
Great for noncirrhotic pts
For cirrhotic pts: wks with RBV reasonable but not ideal concern that failure will affect future options
SOF/LDV + RBV
Better than expected; similar to SOF + DCV for noncirrhotics but RBV clearly needed
DCV, daclatasvir; pegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response.
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17. AASLD/IDSA Guideline Recommendations: Genotype 3 HCV
Prior Treatment
No Cirrhosis
Compensated Cirrhosis
Naive
SOF + DCV for 12 wks
SOF + pegIFN/RBV for 12 wks
SOF + RBV for 24 wks
SOF + DCV ± RBV for 24 wks
SOF + pegIFN/RBV for 12 wks
Experienced
PegIFN/RBV
SOF + RBV
SOF + DCV + RBV for 24 wks
AASLD, American Association for the Study of Liver Disease; DCV, daclatasvir; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; pegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir.
Bold = recommended regimen.
Decompensated cirrhosis
SOF + DCV + low-initial dose RBV for 12 wks
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

18. What’s Coming?

19. Pangenotypic Treatment Option Coming Soon
ASTRAL 3: SOF + velpatasvir (GS-5816) (NS5A) for 12 wks vs SOF + RBV for 24 wks in
treatment-naive and treatment-experienced pts with GT3 HCV
SOF + RBV for 24 Wks
SOF/VEL for 12 Wks
100 98
100 90 93 91 89 80 73 80 71 60 58 60
SVR12 (%)
SVR12 (%) 40 40
GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. 20 20
141/ 156
33/ 45
22/ 31
22/ 38
160/ 163
40/ 43
31/ 34
33/ 37
n/N =
F0-3
Cirrhosis
F0-3
Cirrhosis
F0-3
Cirrhosis
F0-3
Cirrhosis
Naive
Experienced
Naive
Experienced
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Foster GR, et al. N Engl J Med. 2015;373:

20. Avoiding Future Failure . . .
ASTRAL 3: SVR12 rate with SOF/VEL relative to presence/absence of NS5A RAVs:
Failing with an NS5A today may impair responses for the future . . .
97% SVR12
88% SVR12
231 (84%) had no baseline NS5A RAVs
43 (16%)
had baseline NS5A RAVs
RAV, resistance association variant; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
225/231
38/43
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Foster GR, et al. N Engl J Med. 2015;373:

21. SOF/VEL Safety (ASTRAL 1)
Pts,* n (%)
Placebo
(n = 116)
SOF/VEL
(n = 624)
All AE
89 (77)
485 (78)
Grade 3/4 AE
1 (< 1)
18 (3)
Serious AE
15 (2)
Discontinued due to AE
2 (2)
Death
Laboratory abnormalities, grade 3/4
14 (12)
45 (7)
Hb < 10 g/dL
2 (< 1)
Hb < 8.5 g/dL
AE, adverse event; GT, genotype; Hb, hemoglobin; HCV, hepatitis C virus; SOF, sofosbuvir; VEL, velpatasvir
*Pts with GT1, 2, 4, 5, 6 HCV.
Headache, fatigue, nausea most common equal for treatment and placebo
Feld JJ, et al. N Engl J Med. 2015;373: Feld JJ, et al. AASLD Abstract LB-2.
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22. Challenges Still Remain . . .
ASTRAL 4: SOF/VEL ± RBV for 12 wks or SOF/VEL for 24 wks in pts with CP-B cirrhosis
SOF/VEL 12 wk SOF/VEL+RBV 12 wk SOF/VEL 24 wk
CTP Score Change From Baseline: Pts With SVR
100 94 85 83 86 50
47% Improved
10% Worsened 50 80 50 43 60 40
SVR12 (%) 31 30 40 20 20 13 10
75/ 90
82/ 87
77/ 90 7/ 14
11/ 13 6/ 12 7 2
< 1
< 1 2
< 1
< 1
AE, adverse event; CTP, Child-Turcotte-Pugh; GT, genotype; LTFU, lost to follow-up; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir.
Overall
GT3 -5 -4 -3 -2 -1 1 2 4 5
Breakthrough, n
Relapse, n
LTFU, n
Death, n 1 2 - 1 7 3 2 - 6 1 1 - 1 4 -
Change in CTP Score
AEs consistent with clinical sequelae of advanced liver disease, RBV toxicity
RBV won’t go away… still helpful in advanced cirrhosis
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Charlton MR, et al. AASLD Abstract LB-13.

23. Would Another Drug Help?
SOF/VEL + GS-9857 (PI) for 6-12 wks in pts with GT3 HCV
100
100 97 94 80 60
SVR12 (%) 40 20
* Treatment-naive pts
†Tx-experienced cirrhotic and noncirrhotic pts
SOF, sofosbuvir; SVR, sustained virologic response; Tx, treatment; VEL, velpatasvir.
21/ 21
17/ 18
34/ 35
n/N =
F0-3
Cirrhosis
12 wks[2]†
6 wks[1]*
8 wks[1]*
Looks promising across genotypes and for retreatment
1. Gane EJ, et al. EASL Abstract SAT Lawitz E, et al. EASL Abstract PS008.
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24. Another Promising New Regimen
SURVEYOR-II:
ABT-493 (PI) + ABT-530 (NS5A) ± RBV for 12 wks in pts with GT3 HCV
100
100
100 93
Safety Outcome,
Cirrhotic Pts
n (%)[2]
ABT ABT-530
(n = 24)
ABT ABT RBV
Any AE
21 (88)
20 (83)
Serious AEs
1 (4)
2 (8)
AEs occurring in ≥ 10% pts
Headache
Fatigue
Nausea
URTI
Dizziness
Diarrhea
3 (13)
4 (17)
5 (21)
8 (33)
6 (25) 80
ABT ABT-530
ABT ABT RBV 60
SVR12 (%) 40
AE, adverse event; GT, genotype; HCV, hepatitis C virus; RBV, ribavirin; SVR, sustained virologic response. 20
28/ 30
24/ 24
24/ 24
n/N =
Non- cirrhotic[1]
Cirrhotic[2]
1. Kwo PY, et al. AASLD Abstract Kwo PY, et al. EASL Abstract LBO1.
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25. Genotypes 2, 4, 5, and 6 HCV
HCV, hepatitis C virus.

26. The Other Genotypes
All have effective regimens with SVR rate > 90%[1]
Goals for future regimens
Ribavirin free
Shorter duration
Ideal regimen
Pangenotypic
Short duration
Well tolerated
SVR, sustained virologic response.
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1. AASLD/IDSA. HCV guidelines. April 2016.

27. Genotype 2 HCV
HCV, hepatitis C virus.

28. Genotype 2 HCV
Initial genotype to have interferon-free, highly effective regimen
Challenges
First-line therapy contains ribavirin
Goal
Ribavirin-free, short-duration regimen
HCV, hepatitis C virus.
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29. AASLD/IDSA Guideline Recommendations: Genotype 2 HCV
Pt Subgroup
SOF + RBV
SOF + DCV
SOF +
PegIFN/RBV
Treatment naive or pegIFN/RBV
failures
Recommended
No cirrhosis: 12 wks Cirrhosis: wks
if RBV ineligible
Alternative
for pegIFN/RBV
failures with cirrhosis
12 wks
AASLD, American Association for the Study of Liver Diseases; DCV, daclatasvir; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; pegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir.
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

30. 12-wk regimen effective in small sample size; 8 wks less effective
SOF + DCV for GT2 HCV
ALLY-2: open-label study that included 19 pts with GT2 HCV
HIV/HCV pts; treatment-naive pts randomized 2:1 to receive either or 8 wks of treatment; previously treated pts received 12 wks of treatment
Regimen: SOF 400 mg + DCV 60 mg daily (with dose adjustment for HIV ARVs); no RBV
SVR12, GT2 HCV
n/N (%)
Naive
12 Wks
8 Wks
Experienced
Combined
Overall
11/11 (100)
5/6 (83)
2/2 (100)
13/13 (100)
Cirrhotic --
1/1 (100)
Noncirrhotic
12/12 (100)
ARV, antiretroviral; DCV, daclatasvir; GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir; SVR, sustained virologic response.
12-wk regimen effective in small sample size; 8 wks less effective
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Wyles DL, et al. N Engl J Med. 2015;373:

31. AASLD/IDSA Guideline Recommendations: Genotype 2 HCV
Pt Subgroup[1]
SOF + RBV
SOF + DCV
SOF +
PegIFN/RBV
Treatment naive or
pegIFN/RBV
failures
Recommended
No cirrhosis: 12 wks Cirrhosis: wks
if RBV ineligible
Alternative
for pegIFN/RBV
failures with cirrhosis
12 wks
SOF + RBV failures* --
± cirrhosis
± RBV 24 wks†
if IFN eligible
12 wks†
AASLD, American Association for the Study of Liver Diseases; DCV, daclatasvir; GT, genotype; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; IFN, interferon; pegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir; Tx, treatment.
*Limited data for genotype 2 SOF failures. †Level C: consensus opinion of experts, case studies, or standard of care.
Recombinant GT2k/1b HCV observed in 15% of pts in analysis of 279 pts in Germany, Israel, and Italy[2]
SOF + RBV appears less effective for these pts; pts may benefit from GT1b Tx
1. AASLD/IDSA. HCV guidelines. April Susser S, et al. EASL Abstract PS001.
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32. What About Sofosbuvir/Velpatasvir?
ASTRAL 2: SOF/VEL vs SOF + RBV for 12 wks in TN/TE pts with GT2 HCV
P = .02
(superiority)
Endpoint, n (%)
SOF/VEL
(n = 134)
SOF + RBV
(n = 132)
Relapse (Wk 12)
6 (5)
Discontinuations due to AE
1 (1)
Serious AEs
2 (1)
2 (2)
Hgb < 10 g/dL 99
100 94 80 60
SVR12 (%)
AE, adverse event; GT, genotype; HCV, hepatitis C virus; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; TE, treatment experienced; TN, treatment naive; VEL, velpatasvir. 40 20
133/134
124/132
SOF/VEL 12 wks
SOF + RBV 12 wks
n/N =
Slide credit: clinicaloptions.com
Foster GR, et al. N Engl J Med. 2015;373:

33. Genotype 4 HCV
HCV, hepatitis C virus.

34. Genotype 4 Multiple highly effective regimens Challenges Goal
Some regimens include ribavirin
Goal
Ribavirin-free, short-duration regimen
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35. AASLD/IDSA Guideline Recommendations: Genotype 4 HCV
Pt Subgroup
OBV/PTV/
RTV
EBV/GRZ
SOF/LDV
SOF + RBV
SOF +
PegIFN/RBV
Treatment naive, ± cirrhosis
Recommended
+ RBV
12 wks --
Alternative
if IFN eligible
failures,
without cirrhosis
Relapse: 12 wks
Others*: + RBV 16 wks
if RBV eligible and IFN ineligible
24 wks
cirrhosis
24 wks or
12 wks + RBV if eligible
AASLD, American Association for the Study of Liver Diseases; HCV, hepatitis C virus; EBV, elbasvir; GRZ, grazoprevir; IDSA, Infectious Diseases Society of America; IFN, interferon; OBV, ombitasvir; pegIFN, peginterferon; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; SOF, sofosbuvir.
*Prior on-treatment failure to suppress or breakthrough.
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AASLD/IDSA. HCV guidelines. April 2016.

36. OBV/PTV/RTV + RBV for GT4 HCV
PEARL-I: guided 12 wks and need for RBV in noncirrhotics[1]
Treatment in compensated cirrhosis?
Regimen: OMB/PTV/RTV + RBV
AGATE-I: 12 vs 16 wks[2]
AGATE-II: 12 vs 24 wks[3]
AASLD/IDSA recommendation: 12 wks + RBV with cirrhosis[4]
100 97 98 97 93 80 60
SVR12 (%) 40
AASLD, American Association for the Study of Liver Diseases; GT, genotype; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; SVR, sustained virologic response. 20
57/ 59
60/ 61
30/ 31
27/ 29
n/N =
12 Wks
16 Wks
12 Wks
24 Wks
1. Hézode C, et al. Lancet. 2015;385: Asselah T, et al. EASL Abstract SAT-278.
3. Waked I, et al. EASL Abstract SAT AASLD/IDSA. HCV guidelines. April 2016.
AGATE-I
AGATE-II
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37. Elbasvir/Grazoprevir for GT4 HCV
Trial, GT4 HCV Pt Subgroup,
% (n/N)
EBV/GRZ
12 Wks
EBV/GRZ + RBV
16 Wks
NAIVE
C-EDGE[1]
100
(18/18) --
C-EDGE HIV/HCV[2] 96
(27/28)
C-SCAPE[3] 90
(9/10)
(10/10)
EXPERIENCED
C-EDGE[4] 78
(7/9) 93
(14/15) 60
(3/5)
(8/8)
EBV, elbasvir; GT, genotype; HCV, hepatitis C virus; GRZ, grazoprevir; RBV, ribavirin; TE, treatment experienced; TN, treatment naive.
12-wk regimen effective for TN pts; longer regimens and/or RBV may be needed for TE pts
1. Zeuzem S, et al. Ann Intern Med. 2015;163: Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e Brown A, et al. EASL Abstract P Kwo PY, et al. EASL Abstract P0886.
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38. Sofosbuvir/Velpatasvir for GT4 HCV
ASTRAL 1: SOF/VEL vs PBO for 12 wks in TN/TE pts with GT1, 2, 4, 5, 6 HCV
Parameter
All GTs on SOF/VEL
(n = 624)
GT4 on SOF/VEL
(n = 116)
Cirrhosis, %
19.4
23.3
SVR12, % (n/N)
99.0
(618/624)
100
(116/116)
GT, genotype; HCV, hepatitis C virus; PBO, placebo; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; TE, treatment experienced; TN, treatment naive; VEL, velpatasvir.
Slide credit: clinicaloptions.com
Feld JJ, et al. N Engl J Med. 2015;373:

39. Genotypes 5 and 6 HCV
HCV, hepatitis C virus.

40. Genotypes 5 and 6 Challenges Goal Limited data
Ribavirin-free, short-duration regimen
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41. AASLD/IDSA Guideline Recommendations: Genotypes 5 and 6 HCV
Pt Subgroup
SOF/LDV
SOF + PegIFN/RBV
Treatment naive,
± cirrhosis
Recommended
12 wks
Alternative
if IFN eligible
PegIFN/RBV failures,
AASLD, American Association for the Study of Liver Diseases; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; IFN, interferon; LDV, ledipasvir; pegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir.
Slide credit: clinicaloptions.com
AASLD/IDSA. HCV guidelines. April 2016.

42. Sofosbuvir/Ledipasvir for GT5 HCV
SOF/LDV for 12 wks in TN/TE pts with GT5 HCV
Open-label, multicenter, single-arm phase II trial
100 95 95 80 60
SVR12 (%) 40
GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; SOF, sofosbuvir; SVR, sustained virologic response; Tx, treatment. 20
20/ 21
19/ 20
n/N =
Naive
Experienced
12-wk SOF/LDV effective for Tx-naive and Tx-experienced pts
Slide credit: clinicaloptions.com
Abergel A, et al. Lancet Infect Dis. 2016;16:

43. What About Elbasvir/Grazoprevir for Genotypes 5 and 6 HCV?
Not currently included in AASLD/IDSA guidance
FDA approval not received for genotype 5 or 6
Genotype 6: limited data
C-EDGE (phase III trial): included 10 treatment-naive pts with genotype 6 HCV[1]
Elbasvir/grazoprevir 12 wks without ribavirin
SVR12 8/10 (80%)
AASLD, American Association for the Study of Liver Diseases; FDA, US Food and Drug Administration; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; SVR, sustained virologic response.
Slide credit: clinicaloptions.com
1. Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

44. Sofosbuvir/Velpatasvir for GT5 and 6 HCV
ASTRAL 1: SOF/VEL vs PBO for 12 wks in TN/TE pts with GT1, 2, 4, 5, 6 HCV
Parameter
All GTs on SOF/VEL
(n = 624)
GT5 on SOF/VEL
(n = 35)
GT6 on SOF/VEL
(n = 41)
Cirrhosis, %
19.4
14.3
14.6
SVR12, % (n/N)
99.0
(618/624)
97.1
(34/35)
100
(41/41)
GT, genotype; HCV, hepatitis C virus; PBO, placebo; SOF, sofosbuvir; SVR, sustained virologic response; TE, treatment experienced; TN, treatment naive; VEL, velpatasvir.
Slide credit: clinicaloptions.com
Feld JJ, et al. N Engl J Med. 2015;373:

45. Summary Genotype 3 HCV Genotypes 2, 4, 5, 6 HCV Noncirrhotics
SOF + DCV for 12 wks very effective
SOF + RBV for 24 wks or SOF + pegIFN/RBV for 12 wks acceptable
Cirrhotics
May consider waiting for promising options in the near future, including:
SOF/VEL ± GS-9857
ABT ABT-530
Genotypes 2, 4, 5, 6 HCV
Effective regimens available
Progress continues with potent, shorter durations
DCV, daclatasvir; HCV, hepatitis C virus; pegIFN, peginterferon; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir.
Slide credit: clinicaloptions.com

46. Go Online for More CCO Content on HCV Management!
Video Modules featuring case-based expert roundtable discussions of key HCV management issues Downloadable PowerPoint slides on other important HCV topics, including strategies for managing patients infected with genotype 1 HCV
clinicaloptions.com/hcv