Study on the Effectiveness of SOF/VEL/VOX vs. SOF/VEL in HCV Treatment
Explore the POLARIS-4 study comparing the efficacy of SOF/VEL/VOX and SOF/VEL treatments in genotypes 1-6 of chronic HCV infection. Results show high SVR rates, especially in patients without cirrhosis, supporting the use of these regimens in DAA-experienced individuals. Baseline characteristics, SVR rates by genotype and cirrhosis status, and data on baseline RASs are provided.
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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 SOF/VEL/VOX 400/100/100 mg QD N = 182 SVR12 SVR12 N = 151SOF/VEL 400/100 mg QD * 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 > 0.75 + 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 Bourli re M. NEJM 2017; 376:2134-46
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 57 21 88 6.3 46 SOF/VEL 12 weeks N = 151 57 25 87 6.3 46 Age, years, mean Female, % White, % HCV RNA, log10IU/mL, mean Cirrhosis, % Genotype, % 1a 1b 2 3 4 Previous DAA treatment , % NS5B inhibitor + NS3 inhibitor NS5B inhibitor NS3 inhibitor 2 regimens Most recent HCV treatment response, % No response / Relapse 30 13 17 30 10 29 14 22 34 0 25 74 1 39 25 72 2 40 4 / 94 8 / 87 POLARIS-4 Bourli re M. NEJM 2017; 376:2134-46
POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience SVR12overall and by cirrhosis status, % (95% CI) SOF/VEL/VOX 12 weeks SOF/VEL 12 weeks 97.8 * (95-99) % 98 90.1 (84-94) 100 94 98 86 80 1 relapse 1 death 2 lost to follow-up 60 1 breakthrough 14 relapses 40 20 182 151 98 No cirrhosis 82 84 Cirrhosis 69 N= 0 Overall * p < 0.001 for superiority compared with prespecified 85% performance goal POLARIS-4 Bourli re M. NEJM 2017; 376:2134-46
POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience SVR12by genotype, % SOF/VEL/VOX 12 weeks SOF/VEL 12 weeks % 100 100 98 97 96 100 95 96 89 85 80 60 40 20 54 44 24 22 31 33 54 52 19 0 N= 0 Genotype 1a Genotype 1b Genotype 2 Genotype 3 Genotype 4 POLARIS-4 Bourli re M. NEJM 2017; 376:2134-46
POLARIS-4 study: SOF/VEL/VOX vs SOF/VEL in genotypes 1 to 6 with non-NS5A inhibitor experience SVR12according to baseline RASs (15% cutoff) SOF/VEL/VOX 12 weeks * SOF/VEL 12 weeks ** N = 179 85/86 (98.8%) N = 151 67/75 (89.3%) No NS3 or NS5A RASs 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 Bourli re M. NEJM 2017; 376:2134-46
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 12 weeks N = 151 At least one adverse event, % Serious treatment-related adverse events, N Discontinuation due to adverse event, N (%) Death Adverse events in > 10% of patients, % Headache Fatigue Diarrhea Nausea 77 4 0 74 4 1 (< 1%) * 0 1 (< 1%) ** 27 24 20 12 28 28 5 8 Laboratory abnormalities, % Grade 3 Grade 4 5 6 < 1 < 1 *1 patient discontinued due to worsening headaches on study D49 ** 1 patient died of an opiate overdose on post-treatment D2 POLARIS-4 Bourli re M. NEJM 2017; 376:2134-46
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, SVR12was 98% for 12 weeks of SOF/VEL/VOX, meeting superiority criteria to prespecified 85% rate SVR12was 90% for 12 weeks of SOF/VEL Lower SVR12rate 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 Bourli re M. NEJM 2017; 376:2134-46
