1. POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
Design
Randomisation*
1 : 1
Open-label
W12
> 18 years Chronic HCV infection
Genotype 1 to 6
Virologic failure after
≥ 4 weeks treatment
DAA-experienced
(exclusion if prior NS5A
or NS3 (PI) + PEG-IFN + RBV)
Compensated cirrhosis ** allowed
N = 182
SOF/VEL/VOX
400/100/100 mg QD
SVR12
SOF/VEL 400/100 mg QD
SVR12
N = 151
* Randomisation in genotypes 1, 2 and 3, stratified on genotype and cirrhosis
No randomisation in other genotypes (open-label SOF/VEL/VOX)
** Metavir F4 or Ishak 5-6 or
Fibroscan > 12.5 kPa or
Fibrotest > APRI > 2
Objective
SVR12 (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-4
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2. Baseline characteristics
POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
Baseline characteristics
SOF/VEL/VOX 12 weeks
N = 182
SOF/VEL 12 weeks N = 151
Age, years, mean 57
Female, % 21 25
White, % 88 87
HCV RNA, log10 IU/mL, mean
6.3
Cirrhosis, % 46
Genotype, % 1a 1b 2 3 4
Previous DAA treatment , %
NS5B inhibitor + NS3 inhibitor
NS5B inhibitor
NS3 inhibitor
≥ 2 regimens
25 74 1 39
25 72 40
Most recent HCV treatment response, %
No response / Relapse
4 / 94
8 / 87
POLARIS-4
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3. SVR12 overall and by cirrhosis status, % (95% CI)
POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
SVR12 overall and by cirrhosis status, % (95% CI)
SOF/VEL/VOX 12 weeks
SOF/VEL 12 weeks %
97.8 *
(95-99)
100 98
90.1
(84-94) 94 98 86 80
1 relapse
1 death
2 lost to follow-up 60
1 breakthrough
14 relapses 40 20 N=
182
151 98 82 84 69
Overall
No cirrhosis
Cirrhosis
* p < for superiority compared with prespecified 85% performance goal
POLARIS-4
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4. POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
SVR12 by genotype, %
SOF/VEL/VOX 12 weeks
SOF/VEL 12 weeks %
100
100 98
100 96 97 95 96 89 85 80 60 40 20 N= 54 44 24 22 31 33 54 52 19
Genotype 1a
Genotype 1b
Genotype 2
Genotype 3
Genotype 4
POLARIS-4
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5. SVR12 according to baseline RASs (15% cutoff)
POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
SVR12 according to baseline RASs (15% cutoff)
SOF/VEL/VOX 12 weeks *
N = 179
SOF/VEL 12 weeks **
N = 151
No NS3 or NS5A RASs
85/86 (98.8%)
67/75 (89.3%)
NS3 RAS only
39/39 (100%)
29/32 (90.6%)
NS5A RAS only
40/40 (100%)
32/34 (94.1%)
NS3 + NS5A RASs
4/4 (100%)
2/4 (50%)
* All 22 patients with baseline NS5B RAS achieved SVR12 ; No treatment-emergent RASs in the patient who relapsed
** All 8 patients with baseline NS5B RAS achieved SVR12 ; 11/14 patients with virologic relapse developed Y93H or Y93C
POLARIS-4
Bourlière M. NEJM 2017; 376:

6. POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
Adverse events
SOF/VEL/VOX
12 weeks
N = 182
SOF/VEL
N = 151
At least one adverse event, % 77 74
Serious treatment-related adverse events, N 4
Discontinuation due to adverse event, N (%)
1 (< 1%) *
Death
1 (< 1%) **
Adverse events in > 10% of patients, %
Headache 27 28
Fatigue 24
Diarrhea 20 5
Nausea 12 8
Laboratory abnormalities, %
Grade 3
Grade 4
< 1 6
*1 patient discontinued due to worsening headaches on study D49
** 1 patient died of an opiate overdose on post-treatment D2
POLARIS-4
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7. POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience
Summary
In a wide variety of DAA-experienced patients, excluding those pre-treated with NS5A inhibitor, with genotypes 1, 2, 3 or 4,
SVR12 was 98% for 12 weeks of SOF/VEL/VOX, meeting superiority criteria to prespecified 85% rate
SVR12 was 90% for 12 weeks of SOF/VEL
Lower SVR12 rate in cirrhotic patients (86% vs 96%)
Baseline RASs did not impact outcome for SOF/VEL/VOX : SVR12 rates of 100%
No treatment-emergent RASs in the patient who relapsed with SOF/VEL/VOX
79% (11/14) patients with virologic failure to SOF/VEL had emergence of Y93H or Y93C
SOF/VEL/VOX and SOF/VEL were well tolerated
SOF/VEL/VOX for 12 weeks provides a simple, safe, and effective single tablet, once daily treatment for NS5B-experienced patients
POLARIS-4
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