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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 263 N 152 W12 Placebo gt 18 years Chronic HCV infection Genotype 1 2 3 4 5 or 6 NS5A inhibitorexperienced for 4 weeks exclusion if discontinued due to an adverse ID: 623567

vel sof polaris patients sof vel patients polaris ns5a 100 vox inhibitor experienced genotype study bourli

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Slide1

SOF/VEL/VOX400/100/100 mg QD

N = 263

N = 152

W12

Placebo

>

18 years

Chronic HCV infectionGenotype 1, 2, 3, 4, 5 or 6NS5A inhibitor-experienced for ≥ 4 weeks (exclusion if discontinued due to an adverseevent or unsuccessful due to non-compliance)Compensated cirrhosis ** allowed

Randomisation*1 : 1Double blind

*

Randomisation

only in genotype 1, stratified on cirrhosis (yes or no) ;

No randomisation (open-label SOF/VEL/VOX) for all other genotypes

SVR12

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

POLARIS-1

Design

ObjectiveSVR12 (HCV RNA < 15 IU/mL), with 95% CI, by ITT: superiority > 10% to a prespecified rate of 85% (2-sided significance level of 5%), for each regimen, 90% power

POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6

Bourlière

M. NEJM 2017; 376:2134-46Slide2

SOF/VEL/VOXN = 263

Placebo

N = 152

Age, years, mean

58

59

Female, %

24

20

White, %

80

82

Genotype, %

1a

1b1 other234

5 / 6 / unknown

38

1722308< 1 / 2 / < 1

77

20

10000 / 1 / 0HCV RNA, log10 IU/mL, mean6.36.3Cirrhosis, %4634Previous HCV treatment, %NS5A + NS3 +± NS5BNS5A + NS5BNS5ANS5B ± NS3≥ 2 regimens32617< 13941536133Discontinuation, N (adverse event / lost to follow-up)2 (1 / 1)3 (3 / 0)

Baseline characteristics and patient disposition

POLARIS-1

POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6

Bourlière

M. NEJM 2017; 376:2134-46Slide3

* Superiority to 85% (p < 0.001)SOF/VEL/VOX 12 weeks: SVR12 overall and by subgroups, % (95% CI)

0

20

40

60

80

100

96.2 *

(93-98)

Total

99

(95-100)

No

121

93

(87-97)

Cirrhosis

150

101

100

(92-100)

4

5

100

6

Genotype

45

5

95

(87-99)

6 relapses

1 on-treatment failure

2 withdrew consent

1 lost to follow-up

1 withdrew consent

1 lost to follow-up

%

6 relapses

1 on-treatment failure

1 withdrew consent

1

3

1b

1a

2

96

(90-99)

100

(48-100)

78

22

6

1

100

(54-100)

263

142

97

91

(71-99)

Yes

POLARIS-1

POLARIS-1 study: SOF/VEL/VOX in NS5A

inhibitor-experienced patients with genotype 1 to 6

N=

Bourlière

M. NEJM 2017; 376:2134-46Slide4

SVR12 by baseline RASs (15% cutoff), %

0

20

40

60

80

100

97.7

97.1

97.2

100

96.8

Any RASs

NS3 only

NS5A only

NS3 + NS5A

No RASs

43

205

9

124

72

%

Two patients had S282T at baseline, both achieved SVR

12

None of the patients who relapsed had treatment-emergent RASs

POLARIS-1

POLARIS-1 study: SOF/VEL/VOX in NS5A

inhibitor-experienced patients with genotype 1 to 6

N=

Bourlière

M. NEJM 2017; 376:2134-46Slide5

Sex, age, raceGenotype

Cirrhosis

HCV

RNA, log10 IU/mL

Prior HCV regimen

Resistance-associated

substitutions

NS3

NS5A

Baseline

Relapse

Baseline

Relapse

M, 61, white

1a

Yes

6.7

LDV/SOF

24W

Q80K

Q80KY93NY93NM, 60, white3aYes7.6SOF/VEL 12WNoneNoneY93Y/HY93HF, 62, White3aYes6.3DCV + SOF 12WNoneNoneA30KA30KM, 65, white3aYes4.9DCV + SOF 25WNoneNone

None

None

M, 60, white

3a

Yes

5.3

SOF/VEL

12W

None

None

Y93Y/H

Y93H

M, 61, white

4d

Yes

5.7

LDV/SOF 12W

None

None

L30R

L30R + Y93H

M, 60, black *

1a

Yes

6.3

LDV/SOF

Q80K

Q80K

Q30T

Q30T + L31L/M + Y93Y/H

*

Only

patient

with

virologic

breakthrough

:

low plasma concentrations of GS-331007 (the chief SOF metabolite), VEL, and VOX at weeks 8 and 12, suggestive of nonadherenceCharacteristics of patients with virologic

failure (n = 7)POLARIS-1POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6 Bourlière M. NEJM 2017; 376:2134-46Slide6

SOF/VEL/VOXN = 263

Placebo

N = 152

At least one adverse

event, %

78

70

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

5 (2%)0

7 (5%)

0

Grade 3-4 adverse events, N (%)

5 (2%)

4

(3%)

Discontinuation due to adverse event, N (%)

1 (< 1%)

Angioedema attributed to ramipril3 (2%)

Death

0

0Adverse events in > 10% of patients, %Headache2517Fatigue2120Diarrhea1812Nausea148Grade 3 / Grade 4 laboratory abnormalities, %5 / 2

12

/ 2

Adverse events

POLARIS-1

POLARIS-1 study: SOF/VEL/VOX in NS5A

inhibitor-experienced patients with genotype 1 to 6

Bourlière

M. NEJM 2017; 376:2134-46Slide7

SummaryIn NS5A-inhibitor experienced patients, treatment with SOF/VEL/VOX for 12 weeks resulted in a 96.2% SVR12 rate in difficult-to-cure patients with multiple unfavorable characteristics Treatment-emergent NS5A RAS was observed in 1/6 patients with relapseSOF/VEL/VOX was well tolerated with an adverse event profile similar to that observed in placebo recipientsSOF/VEL/VOX for 12 weeks provides a single tablet, once daily, highly effective, RBV-free treatment for NS5A inhibitor-experienced patients

POLARIS-1

POLARIS-1 study: SOF/VEL/VOX in NS5A inhibitor-experienced patients with genotype 1 to 6

Bourlière M. NEJM 2017; 376:2134-46

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