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SOF/VEL/VOX SOF/VEL/VOX

SOF/VEL/VOX - PowerPoint Presentation

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SOF/VEL/VOX - PPT Presentation

400100100 mg QD N 501 N 440 W8 SOFVEL 400100 mg QD gt 18 years Chronic HCV infection Genotype 1 2 3 4 5 or 6 Treatmentnaïve or IFNexperienced Compensated cirrhosis allowed ID: 556976

sof vel genotype weeks vel sof weeks genotype vox patients polaris 100 relapses jacobson study march 2017 svr12 follow

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Slide1

SOF/VEL/VOX400/100/100 mg QD

N = 501

N = 440

W8

SOF/VEL 400/100 mg QD

>

18 years

Chronic HCV infectionGenotype 1, 2, 3, 4, 5 or 6Treatment-naïve or IFN-experiencedCompensated cirrhosis ** allowed (exclusion of genotype 3 with cirrhosis)

Randomisation*1 : 1Open-label

*

Randomisation

only in genotype 1, 2, 3 and 4, stratified on genotype, cirrhosis (yes or no) and prior treatment-experience (naïve or IFN-experienced) ; No randomisation (open-label SOF/VEL/VOX) for other genotypes

SVR12

** Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa or Fibrotest  > 0.75 + APRI > 2

POLARIS-2

Design

ObjectiveSVR12 (HCV RNA < 15 IU/mL), by ITT: non-inferiority of SOF/VEL/VOX (wo-sided significance level of 5%, lower margin of the 95% CI for the difference = -5%, 95% power)

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

Jacobson IM. Gastroenterology 2017; 153:113-22

W12

SVR

12Slide2

SOF/VEL/VOX8 weeks

N = 501

SOF/VEL

12 weeksN = 440

Age, years, mean

53

55

Female, %49

46

White / Black,

%

78 / 10

83 / 11

Genotype, %

1a1b1 other2345 /

6 / unknown

34

13< 11318134 / 6 / < 1

39

13< 112

20

130 / 2 / 0

HCV RNA,

log

10 IU/mL, mean6.16.2IL28B CC, %3331Cirrhosis, %1819IFN-experienced, %2423Discontinuation, N Adverse event / lost to follow-up / pregnancy10 / 0 / 132 / 1 / 0

Baseline characteristics and patient disposition

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

Jacobson IM.

Gastroenterology

2017; 153:113-22Slide3

SVR12 overall and in genotype 1, %

0

20

40

60

80

100

95 *

Overall

98

233

93

232

169

99

63

172

Genotype 1b

97

21 relapses

4 lost to follow-up

3 relapses

1 discontinuation for AE

4 lost to follow-up

%

16 relapses

Genotype 1

Genotype 1a

92

97

59

501

440

98

2 relapses

2 lost to follow-up

14 relapses

2 relapses

1 relapse

1 lost to follow-up

1 relapse

1 lost to follow-up

SOF/VEL/VOX 8 weeks

SOF/VEL 12 weeks

* Difference (2-sided 95% CI) : -3.4 % (-6.2% to -0.6%)

non inferiority not met

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

N=

Jacobson IM.

Gastroenterology

2017; 153:113-22Slide4

SVR12 in genotype 2 to 6, %

0

20

40

60

80

100

97

Genotype 2

100

92

99

89

63

98

18

57

Genotype 5

100

2 relapses

1 lost to follow-up

%

Genotype 3

Genotype 4

92

94

63

53

97

1 discontinuation for AE

2 lost to follow-up

2 relapses

3 lost to follow-up

1 relapse

100

100

0

30

2

9

0

1 relapse

Genotype 6

Unknown

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

SOF/VEL/VOX 8 weeks

SOF/VEL 12 weeks

N=

Jacobson IM.

Gastroenterology

2017; 153:113-22Slide5

CirrhosisN = 174No CirrhosisN = 767SVR12 by cirrhosis status, %

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

SOF/VEL/VOX 8 weeks

SOF/VEL 12 weeks

0

20

40

60

80

100

96

98

91

%

99

N=

84

411

90

356

7 relapses

1 LTFU

1 relapse

14 relapses

3 LTFU

2 relapses

4 LTFU

1 DC due to AE

Jacobson IM. AASLD 2016, Abs. LB-12 ; Jacobson

IM. Gastroenterology 2017; 153:113-22Slide6

SVR12 by baseline RASs, %

Any

RASs

NS3

only

NS5A

only

NS3 + NS5A

No

RASs

All 64 patients with baseline NS5B nucleoside inhibitor RASs achieved SVR

12

Any

RASs

NS3

only

NS5A

only

NS3 +

NS5A

No

RASs

0

20

406080100

98

94

100

95

228

250

110

120

19

%

99

99

100

100

218

97

921

30

208

91

99

* RASs were analyzed using a 15% cut off

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

SOF/VEL/VOX 8 weeks

SOF/VEL 12 weeks

N=

Jacobson IM.

Gastroenterology 2017; 153:113-22Slide7

Impact of baseline NS5A RASFor patients with genotype 1a, SVR12 with SOF/VEL/VOX 8 weeks89% if baseline RASs95% if no baseline RASs88% if baseline Q80K94% if absence of baseline 80KViral resistance testing at failureOf the 21 patients who relapsed in the SOF/VEL/VOX group, 1 had treatment-emergent NS5A resistance-associated substitutions Q30R and L31M Among patients receiving SOF/VEL, 1

of the 3 patients who relapsed had the Y93N variant, which is associated with resistance to NS5A inhibitors, at relapse

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

Jacobson IM. Gastroenterology 2017; 153:113-22Slide8

SOF/VEL/VOX8 weeks

N = 501

SOF/VEL

12 weeksN = 440

At least one adverse

event, %

72

69Serious adverse events, N (%)related to study drug

15 (3%)0

7 (2%)

0

Grade 3-4 adverse events, N (%)

11 (2%)

6 (1%)

Discontinuation due to adverse event, N (%)

0

2 (< 1%) *

Death0

0

Adverse

events in

> 5%

of patients, %

Headache

2723Fatigue2120Diarrhea187Nausea169Asthenia6

6

Insomnia

5

5

Arthralgia

4

5

Grade 3-4 laboratory abnormalities,

%

Hemoglobin < 10 g/dl

ALT > 5 x ULN / AST >

5 x ULN

5

1

0 / < 1

4

1

< 1 / 0

Adverse events

*1 upper respiratory tract infection and 1

Clostridium difficile

infection, both not related to the study medication

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

Jacobson IM.

Gastroenterology 2017; 153:113-22Slide9

SummarySOF/VEL/VOX for 8 weeks resulted in a 95% SVR12 rate in DAA-naïve genotype 1-6 patients with and without cirrhosisDid not meet non-inferiority as compared to the 98% SVR12 rate with SOF/VEL for 12 weeksThe difference between the regimens was largely attributed to more relapses among patients with genotype 1a infection in the SOF/VEL/VOX groupSOF/VEL/VOX and SOF/VEL were safe and well toleratedMild gastrointestinal adverse events (nausea and diarrhea) were associated with treatment regimens that included VOXThere was no evidence of VOX-related hepatotoxicityThese findings in DAA-naïve patients with or without cirrhosis underscore the very high rates of SVR conferred by SOF/VEL across all HCV genotypesSOF/VEL/VOX for 8 weeks provides a highly efficacious and well-tolerated short-duration regimen in patients for whom adherence to a longer duration regimen may be challenging

POLARIS-2

POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6

Jacobson IM. AASLD 2016, Abs. LB-12 ; Jacobson IM.

Gastroenterology 2017; 153:113-22

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