treatment of genotype 2, 3 ,4, and...

David E. Bernstein, MD, FACG

Treatment of Genotype 2, 3 ,4, and Beyond

David E. Bernstein, MD, FACGVice Chairman of Medicine for Clinical Trials

Chief, Division of Hepatology and Sandra Atlas Bass Center for Liver DiseasesNorthwell Health System

Professor of MedicineHofstra Northwell School of Medicine

2

Global Prevalence of HCV

Messina JP, et al. Hepatology 2015; 61:77–87.* Excludes Oceania.

46.2

9.1

30.1

8.3

0.85.4

0

10

20

30

40

50

GT1 GT2 GT3 GT4 GT5 GT6

Tota

l glo

bal H

CV se

ropr

eval

ence

(%)

ACG 2016 Southern Hepatitis School Copyright 2016 American College of Gastroenterology

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TREATMENT OF GENOTYPE 2

Therapies for Genotype 2

Treatment Duration (weeks)

Naïve:No cirrhosis

Naïve: Cirrhosis Treatment Experienced: No cirrhosis

TreatmentExperienced: Cirrhosis

SVR

Sofosbuvir/Daclatasvir 12 X X Limited data

Sofosbuvir/Daclatasvir 16-24 X X Limited data

Sofosbuvir/Velpatasvir 12 X X X X 99-100%

http://www.hcvguidelines.org (accessed August 4, 2016), Epclusa Package insert Gilead 6/16, Wyles et al. NEJM 2015 Sulkowski et al NEJM 2014


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Sofosbuvir + Velpatasvir

1. Jacobson IM, et al. New Engl J Med 2013;368:1867-77; 2. Lawitz E, et al. New Engl J Med 2013;368:1878-87; 3. Cheng G, et al. EASL 2013, poster 1191; 4. German P, et al. EASL 2013, poster 1195; 5. Lawitz E, et al. EASL 2013, poster 1082. 6. Everson G, et al. EASL 2014, oral presentation. 3

SOF Nucleotide polymerase inhibitor

♦ Sofosbuvir (SOF)1,2

‒ Potent antiviral activity against HCV GT 1‒6

‒ Once-daily, oral, 400-mg tablet

♦ Velpatasvir3-5

– Picomolar potency against HCV GT 1‒6– PK supports once-daily dosing

♦ SOF + Velpatasvir6

– Treatment for 12 weeks resulted in high SVR in treatment-naïve patients with HCV GT 1‒6 without cirrhosis

GS-5816NS5A inhibitor

SOF GS-5816+

The ASTRAL Phase 3 Program (N=1408)

6

ASTRAL-1GT 1, 2, 4‒6

TN, TENC, CC

ASTRAL-2GT 2

TN, TENC, CC

ASTRAL-3GT 3

TN, TENC, CC

ASTRAL-4GT 1‒6TN, TE

CTP-B Cirrhosis

‡

Primary endpoints– SVR12– Discontinuations due to AEs

n=624

n=116

Wk 0 Wk 12

n=134

n=132

Wk 0 Wk 12

n=277

n=275

Wk 0 Wk 12

SOF + RBV

SOF/VEL

Wk 24 Wk 0

Wk 12

SOF/VEL

Wk 24

n=90

n=87

n=90

SOF/VEL+ RBV

SOF/VEL

SOF/VEL

Placebo

SOF/VEL

SOF+RBV

ASTRAL-5

GT 1‒4

TN, TE

NC, CCHIV/HCV Co-Infection

n=106

Wk 0 Wk 12

SOF/VEL

Feld, AASLD, 2015, LB-2. Feld JJ, et al. N Engl J Med. 2015; Sulkowski, AASLD, 2015, 205. Foster GR, et al. New Engl J Med. 2015.; Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med. 2015, Charlton, AASLD, 2015, LB-13. Curry MP, et al. New Engl J Med.2015. Wyles, EASL 2016, PS104


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SOF/VEL SVR Rates:GT 2 SUBJECTS IN ASTRAL-1 AND ASTRAL-2

100% 99% 94%

0

20

40

60

80

100

SOF + RBV12 WEEKS

SVR1

2, %

ASTR

AL-1

ASTR

AL-2

ASTR

AL-2

133134

104104

124132

EPCLUSA12 WEEKS

• The relapse rate was 0% (0/238) among subjects receiving EPCLUSA for 12 weeks and 5% (6/132) among subjects receiving SOF + RBV for 12 weeks

EPCLUSA US full Prescribing Information. Gilead Sciences, Inc. Foster City, CA. June 2016

ASTRAL-4: Sofosbuvir/Velpatasvir in Decompensated Cirrhosis

• Open-label trial; HCC and liver transplantation excluded

Charlton MR, et al. AASLD 2015. Abstract LB-13.Curry MP, et al. N Engl J Med. 2015;[Epub ahead of print].

All Pts 1 3

HCV Genotype

n/N =

SV

R12

(%

)

SOF/VEL 12 wks SOF/VEL + RBV 12 wks SOF/VEL 24 wks

2, 4, and 6

100

80

60

40

20

0

8394

86 8896 92

50

85

50

100 10086

75/90

82/87

77/90

60/68

65/68

65/71

7/14

11/13

6/12

8/8

6/6

6/7


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NoCirrhosis

CompensatedCirrhosis

Sofosbuvir/velpatasvir (400/100 mg qd) 12 12

Genotype 2: Recommended HCV Regimens forTreatment-Naïve and PEG/RBV Treatment-

Experienced

Duration of Therapy (weeks)

AASLD-IDSA. http://www.hcvguidelines.org/full-report-view. July 6, 2016.

NEW TREATMENTS OF GENOTYPE 2


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ABT-493 + ABT-530 in G2

• SURVEYOR-II: 70% G2b, 87% TN, 82% F0-F1

Poordad F, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. SAT-157.

P/R. pegIFN/RBv; pegIFN, pegylated interferon; RBV, ribavirin.

SURVEYOR-II Study Design8-week Treatment Arms Only

0 8 24

ABT-493 (300 mg)+ ABT-530 (120 mg)

SURVERYOR-IIG2 without cirrhosis

• Open-label study• Treatment-naïve or

P/R experienced

SVR12

Week

ABT-493 + ABT-530: SVR Rates after 8 weeks of Treatment

Poordad F, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. SAT-157.

98

0

20

40

60

80

100

GT2

SVR

12 IT

T (%

)

3334

5354

ABT-493 (300mg) + ABT-530 (120mg)8weeks

100

0

20

40

60

80

100

GT2

SVR

12 m

ITT

(%)

3333

5353

ABT-493 (300mg) + ABT-530 (120mg)8weeks


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TREATMENT OF GENOTYPE 2: WHAT TO DO WITH DAA FAILURES

SOF/VEL + GS-9857 (VOX) - Study Design

• GS-9857 – voxilaprevir Protease inhibitor• Two Phase 2, multicenter, open-label studies

(US, New Zealand) – GS-US-367-1168: G1 – GS-US-367-1169: G2, 3, 4, 5, 6

• Broad inclusion criteria– HCV treatment experienced, including DAA experienced

• G1: NS5A inhibitor or ≥2 DAA classes • G2–6: Peg-IFN + RBV or any DAA

– 50% with compensated cirrhosis

0 12 24

SVR12SOF/VEL + GS-9857N=128

Week

Lawitz E, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. PS008.


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99 100 100 97 100

0

20

40

60

80

100

SVR12 Overall and by Genotype

• One patient relapsed at post-treatment week 8– 58-year-old white female with G3a infection, HCV RNA 7.0 log10 IU/mL, and cirrhosis

SV

R1

2 (

%)

Overall G3G2 G4, 6G1

63/63127/128 9/934/3521/21

Lawitz E, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. PS008.

THERAPY FOR GENOTYPE 3


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Genotype 3 Is Associated With a Significantly Higher Risk of Cirrhosis and HCC vs GT 1

• VA HCV Clinical Case Registry (2000-2009)– 88,348 patients with genotype 1 (80%)

– 13,077 genotype 2 (12%)

– 8,337 genotype 3 (7.5%)

– Mean follow-up 5.4 years

Conclusion: GT 3 is associated with a significantly higher risk of cirrhosis and HCC vs GT 1, independent of age, diabetes, BMI or antiviral treatment

Kanwal F et al, Hepatology 2014;60:98-105

Hazard RatioConfidence

Interval

Cirrhosis 1.31 1.22-1.39

HCC 1.80 1.61-2.03



Naïve: No cirrhosis

Naïve: Compensated cirrhosis

Treatment Experienced: No cirrhosis

Treatment experienced: Compensated Cirrhosis

SVR

Sofosbuvir/Daclatasvir 12 X X 94-97%Sofosbuvir/Daclatasvir/+/-Ribavirin**

24 X 86%

Sofosbuvir/Daclatasvir/+/-Ribavirin

X Limited data

Sofosbuvir/Velpatasvir 12 X 98%Sofosbuvir/Velpatasvir/+/- ribavirin**

12 X 94%

Sofosbuvir/Velpatasvir 12 X 93%Sofosbuvir/Velpatasvir 12 X 89%

Nelson et al. Hepatology 2015, http://www.hcvguidelines.org (accessed August 4, 2016),Epclusa package insert Gilead 6/16

**RAV testing is indicated for Y93H and add ribavirin if present


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Follow-upDCV 60 mg +SOF 400 mg QD

Day 1 Week 24 Week 36

DCV 60 mg +SOF 400 mg QD

Week 12

Treatment-naiveN = 101

Treatment-experiencedN = 51

SVR12

Genotype 3: ALLY-3 Study Design

• Primary endpoint: SVR12• Eligible patients

– Age ≥ 18 years with chronic GT 3 infection and HCV RNA ≥ 10,000 IU/mL– Treatment-naive or -experienced (prior treatment failures), including patients

with cirrhosis– Those who received prior treatment with NS5A inhibitors were excluded

Nelson et al. Hepatology 2015; 61:1127-35

0

20

40

60

80

100 90 86

SV

R12

(%

)

Treatment-naive Treatment-experienced

91/101 44/51

DCV/SOF for GT 3: SVR12 in Treatment-naïve and Treatment-experienced patients Treated for 12 Weeks (ALLY-3)

Nelson DR, Hepatology 2015; 61: 1127-1135


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96 97 94

63 5869

0

20

40

60

80

100

SV

R12

(%)

YesNo

Cirrhosis

YesNo YesNo

Overall Tx-naive Tx-experienced

SVR12 in Patients With and Without Cirrhosis Treated for 12 Weeks (ALLY-3)

Nelson DR, Hepatology 2015; 61: 1127-1135

Ally-3 and Ally-3+: SVR 12 in advanced fibrosis

22

All 12 week 16 week12 week

93

SVR1

2 (%

) + 9

5% C

I

ALLY-3(DCV+SOF)

ALLY-3+(DCV+SOF+RBV)

0102030405060708090

100100

1 relapsePrior SOF+RBV failure

NS5A-Y93H at baselineBaseline HCV RNA:

8.8 × 106 IU/mL

1415

1414

66

88

100 100

Kowdley et el. EASL 2016


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ALLY-3 and ALLY-3+: SVR in Compensated Cirrhosis

23

0102030405060708090

100

64

86 83 89

2133

3136

1518

1618

ALLY-3+(DCV+SOF+RBV)

ALLY-3(DCV+SOF)

All 12 week 16 week12 weekVirologic Failure 12 4 2 2

Breakthrough 0 0 0 0Relapse 11 4 2 2Other (Detectable at EOT) 1 0 0 0

Non-virologic failure (death)a 0 1 1 0aDilated cardiomyopathy on Day 72 (not related to treatment)

SVR1

2 (%

) + 9

5% C

I

Kowdley et al. EASL 2016

Resistance Associated NS5A Variants at Baseline and Failure in Patients with cirrhosis

■ Across both studies, Y93H was present in 12/13 cirrhotic patients with available post-failure sequence data– Emergent in 8, present at baseline in 4

■ No SOF-associated RAVs in NS5B were observed at baseline or relapse– S282T or any substitution at L159, L320, or V321

Resistance assessed by population sequencing (sensitivity ≥ 10%)

No NS5A RAVs

n = 26

NS5ARAVsn = 7

14

Y93H

A30S+Y93H

A30K

A30TSVR12without

RAVs73%

(19/26)

4550

No NS5A RAVs

n = 12NS5A RAVs

n = 2 A30K(n = 4)

Y93H

A30T (n=1)

SVR12without

RAVs90%

(26/29)A30A/V+Y93Y/H

A30K

Y93H

Y93Y/HALLY-3 ALLY-3+

No NS5A RAVs

n = 29

NS5ARAVsn = 6

ALLY-3+ data excludes one patient without RAVs whodied of dilated cardiomyopathy on Day 72, unrelated to

treatment.

One relapse without A30K or Y93H had baseline M28I polymorphism not present at failure. M28I does not affect DCV susceptibility in vitro.

Two ALLY-3 patients with virologic failure had two AVs at baseline (indicated in yellow)

Achieved SVR12 Did not achieve SVR12

Kowdley et al. EASL 2016


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The ASTRAL Phase 3 Program

25

ASTRAL-1GT 1, 2, 4‒6

TN, TENC, CC

ASTRAL-2GT 2

TN, TENC, CC

ASTRAL-3GT 3

TN, TENC, CC

ASTRAL-4GT 1‒6TN, TE

CTP-B Cirrhosis

‡

Primary endpoints– SVR12– Discontinuations due to AEs

n=624

n=116

Wk 0 Wk 12

n=134

n=132

Wk 0 Wk 12

n=277

n=275

Wk 0 Wk 12

SOF + RBV

SOF/VEL

Wk 24 Wk 0

Wk 12

SOF/VEL

Wk 24

n=90

n=87

n=90

SOF/VEL+ RBV

SOF/VEL

SOF/VEL

Placebo

SOF/VEL

SOF+RBV

ASTRAL-5

GT 1‒4

TN, TE

NC, CCHIV/HCV Co-Infection

n=106

Wk 0 Wk 12

SOF/VEL

Feld, AASLD, 2015, LB-2. Feld JJ, et al. N Engl J Med. 2015; Sulkowski, AASLD, 2015, 205. Foster GR, et al. New Engl J Med. 2015.; Mangia, AASLD, 2015, 249. Foster GR, et al. New Engl J Med. 2015, Charlton, AASLD, 2015, LB-13. Curry MP, et al. New Engl J Med.2015. Wyles, EASL 2016, PS104

Study DesignASTRAL-3

• Open-label, active-comparator trial • Broad inclusion criteria• 1:1 randomization to SOF/VEL or SOF + RBV

– Stratified by prior treatment (TN/TE) and cirrhosis (presence/absence)• Conducted at 76 sites in US, Canada, UK, Germany, France, Italy, Australia,

and New Zealand

Foster et al. NEJM 2016 26

n=250

n=250

Week 0 12 24

SVR12

SVR12SOF + RBV

36

SOF/VEL


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*p-value for superiority of SOF/VEL compared with SOF+ RBV. Error bars represent 95% confidence intervals.

Results: SVR12ASTRAL-3

27

95

80

0

20

40

60

80

100SV

R12

(%)

264/277 221/275

p <0.001*

SOF/VEL12 Weeks

SOF + RBV24 Weeks

Foster et al NEJM 2016

97 91 97 9087

66

86

63

0

20

40

60

80

100

SOF/VEL SOF + RBV

SVR1

2 (%

)

Results: SVR12 by Cirrhosis or Treatment HistoryASTRAL-3

Error bars represent 95% confidence intervals.

191197

7380

5583

200206

176204

6471

4571

163187

No Yes Naïve Experienced

Cirrhosis Status Treatment History

28NEJM 2016


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Results: Resistance AnalysisASTRAL-3: SOF/VEL Group

• SVR12 was 84% (21/25) in patients with Y93H

Foster NEJM 2016 29

84% No BL

NS5A RAVsn=231

16% BL NS5A

RAVsn=43

Total, n=274

97% SVR12

225/231

88% SVR12

38/43

NoCirrhosis


Sofosbuvir/velpatasvir (400/100 mg qd) + RBV 12(no RBV)

12(+ RBV)*

Daclatasvir (60 mg qd)† + sofosbuvir (400 mg qd)+ RBV

12(no RBV)

24(+ RBV)

AASLD-IDSA: Recommended HCV Regimens forTreatment-Naïve, Genotype 3


*RAV testing for Y93H is recommended for cirrhotic patients and RBV should be included if Y93H is present.†Dose may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).



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AASLD-IDSA: Recommended HCV Regimens forPrior PR Failure, Genotype 3



NoCirrhosis


Sofosbuvir/velpatasvir (400/100 mg qd) + RBV 12(+ RBV)*

12(with RBV)

Daclatasvir (60 mg qd)† + sofosbuvir (400 mg qd)+ RBV

12(+ RBV)*

24(with RBV)

*RAV testing for Y93H is recommended for non-cirrhotic patients and RBV should be included if Y93H is present.†Dose may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).PR: pegIFN/RBV.

NEW THERAPIES ON THE HORIZON FOR GENOTYPE 3


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C-Crest 1 & 2: Part B: MK-3682/GRZ/MK-8408 with and without RBV in non-cirrhotic and cirrhotics with genotype 1,2, and 3

95

98

87

96

100 100 100

98

100

97

80

82

84

86

88

90

92

94

96

98

100

GT 1a GT 1b G2 G3

Per Protocol Analysis

8 weeks 12 weeks 16 weeks

Lawitz et al. AASLD 2016. abstract 110

C-Crest 1 & 2: Part B: MK-3682/GRZ/MK-8408 with and without RBV in non-cirrhotic and cirrhotics with genotype 3

94

95

96

97

98

99

100

101

TN TE

GT3 BY PRIOR TREATMENT EXPERIENCE

8 weeks 12 weeks 16 weeks

Lawitz et al AASLD 2016; abstract 110


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C-Crest 1 & 2: Part B: MK-3682/GRZ/MK-8408 with and without RBV in G3 cirrhotics

100 100 100

96

94

95

96

97

98

99

100

12 week, No RBV 12 week, RBV 16 week, No RBV 16 week, RBV

Lawitz et al. AASLD 2016; abstract 110

ABT-493 (glecaprevir) + ABT-530 (pibrenasvir) SVR Rate – G3 Non-cirrhotics

• No virologic failures• 1 patient withdrew consent after

treatment week 6 due to intolerance of blood draws and had an undetectable HCV RNA at the time of discontinuation

• Safe and well tolerated

Muir AJ, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. PS098.

mITT SVR12 rate excludes non-virologic failures

97 100

0

20

40

60

80

100

.SVR12 mITTSVR12

SVR1

2, %

Pat

ient

s

28 / 29

28 / 28


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Kwo P, et al. 51st EASL; Barcelona, Spain; April 13-17, 2016. Abst. LB01.

ABT-493 + ABT-530 :Genotype 3 Cirrhotics SVR 12 by ITT Analysis

100 100

0

20

40

60

80

100

.ABT-493+ ABT-530

ABT-493+ ABT-530 + RBV

SVR1

2, %

Pat

ient

s

24 /24

24 / 24

Surveyor –II, part 3: Glecaprevir/pibrenasvir in genotype 3

• Non-cirrhotic, TE subjects• Cirrhotics, regardless of Naïve or TE

Non-cirrhotic TE SVR12 weeks 91% (n=22)16 weeks 96% (n=22)

Cirrhotics SVRTN 12 weeks 98%TE 16 weeks 96%

Wyles et al. AASLD 2016, abstract 113


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Polaris 3: SOF/VEL/VOX vs SOF/VEL for genotype 3 and cirrhosis

• Genotype 3, cirrhotic• Two arms

– SOF/VEL/VOX for 8 weeks– SOF/VEL for 12 weeks

• 30% failed previous IFN tx• 219 patients• All Y93H had SVR

– 6 in SOF/VEL/VOX– 4 in SOF/VEL

• No treatment emergent RAS’s developed

0

10

20

30

40

50

60

70

80

90

100

SOF/VEL VOX 8wks

SOF/VEL 12wks

SVR rates96% 96%

Foster et al. AASLD 2016 Abstract 258

TREATMENT OF GENOTYPE 4


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Genotype 4

•Accounts for about 1-2% of HCV infections in U.S.•Common in Egypt, Saudi Arabia, North Africa, and Southern Europe and immigrants from these regions

•Approximately 70% of patients with genotype 4 HCV have moderate to severe steatosis with or without sinusoidal fibrosis (similar to GT3)

•Historic SVR rates with IFN-based therapy between GT1 and GT 2,3



Naïve:No cirrhosis

Naïve:cirrhosis

Treatment Experienced: No cirrhosis

Treatment Experienced-Cirrhosis

SVR

Grazeprevir/Elbasvir 12 X X 97%Grazeprevir/Elbasvir/Ribavirin

16 X X 100%

Paritaprevir/ritonavir/Ombitasvir/Ribavirin

12 X X X X 100%

Sofosbuvir/Ledipasvir 12 X X X X 94%Sofosbuvir/Velpatasvir 12 X X X X 100%

Zepatier Package Insert MSD Ireland 1/16, Technivie Package Insert Abbvie 6/16, Harvoni package insert Gilead 6/16Epclusa package insert Gilead 6/16


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PEARL-I Study: Ombitasvir/Paritaprevir/r + RBV in HCV Genotype 4

• Open-label, phase 2b study– Ombitasvir/paritaprevir/r + RBV

for 12 weeks– Treatment-naïve and

experienced (no prior DAAs)• HCV RNA: 6.1 IU/mL

– No cirrhosis– Primary efficacy endpoint: SVR12

• Baseline NS5A RAVs (58% of patients) did not impact SVR12 rates

• Virologic failures (n=3)– Genotype 4d

0

20

40

60

80

100

SV

R12

(%

)

91%100%

Ombitasvir/Paritaprevir/r

(n=44)

100%

SVR Rates

Hezode C, et al. Lancet. 2015;385:2502-2509.

Ombitasvir/Paritaprevir/r+ RBV (n=42)

Ombitasvir/Paritaprevir/r+ RBV (n=49)

TreatmentNaive

TreatmentExperienced

Astral 1: Velpatasvir (NS5A) + SOF for 12 weeks- Genotype 4, 5 and 6

100 97 100

0

20

40

60

80

100

GT 4 GT 5 GT 6

SVR

Feld et al. NELM 2015

116/116 34/35 41/41


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NoCirrhosis



Ledipasvir/sofosbuvir (90/400 mg qd) 12 12

Elbasvir/grazoprevir (50/100 mg) 12 12

Ombitasvir/paritaprevir/r (25/150/100 mg qd) + RBV 12 12

AASLD-IDSA: Recommended HCV Regimens forTreatment-Naïve, Genotype 4


Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).


NoCirrhosis




Elbasvir/grazoprevir (50/100 mg) 16 16

Ombitasvir/paritaprevir/r (25/150/100 mg qd) + RBV 12 12

AASLD-IDSA: Recommended HCV Regimens forTreatment-Experienced, Genotype 4


Weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]).



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NEW TREATMENTS OF GENOTYPE 4

Surveyor-II, Part 4: Glecaprevir/pibrentasvir in genotype 2,4,5,6 without cirrhosis

• 203 subjects treated for 8 weeks

97

98

100 100

95.5

96

96.5

97

97.5

98

98.5

99

99.5

100

G2 G4 G5 G6

SVR

141/145 44/45 2/2 10/10Hassenian et al. AASLD 2016. Abstract LB-15


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Endurance 4: Glecaprevir/pibrentasvir for genotype 4, 5 ,6

• Non-cirrhotics• 12 week regimen• 99% (120/121) of GT 4-6 patients achieved SVR

Asselah et al. AASLD 2016; Abstract 114

TREATMENT OF GENOTYPE 5 AND 6


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NoCirrhosis




Genotype 5 and 6:Recommended HCV Regimens for

Treatment-Naïve and PEG/RBV Treatment Experienced, Genotype 5 and 6



General Outcomes With AASLD-IDSA Recommended HCV Regimens for Genotype 5 and 6 Patients

Genotype 5: Treatment-Naïve, Treatment-Experienced

Sofosbuvir/velpatasvir: 12 weeks (ASTRAL-1).Ledipasvir/sofosbuvir (12 weeks): genotype 5 (study 1119) and genotype 6 (ELECTRON).

Feld JJ, et al. N Engl J Med. 2015;373:2599-2697.Abergel A, et al. Lancet Infect Dis. 2016;16:459-464.Gane EJ, et al. Gastroenterology. 2015;149:1454-1461.

Percent (n/N)

SVR12Rate

Relapse Rate

DiscontinuationsDue to Adverse Events

Sofosbuvir/velpatasvir 12 weeksNo cirrhosis/compensated cirrhosis 96 (23/24) 0 (0/24) 0 (0/24)

Ledipasvir/sofosbuvir 12 weeksNo cirrhosisCompensated cirrhosis

97 (31/32)

89 (8/9)

3 (1/32)

11 (1/9)

0 (0/32)

0 (0/9)

Sofosbuvir/velpatasvir 12 weeksNo cirrhosis/compensated cirrhosis 100 (38/38) 0 (0/38) 0 (0/38)

Ledipasvir/sofosbuvir 12 weeksNo cirrhosis/compensated cirrhosis 96 (24/25) 4 (1/25) 0 (0/25)

Genotype 6: Treatment-Naïve, Treatment-Experienced


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Summary

• All oral DAA’s highly effective for all non-genotype 1 genotypes• What’s ahead in the future

– Pangenotypic therapies– Shorter duration of treatment?


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treatment of genotype 2, 3 ,4, and...

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