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Design Randomisation* 1 : 1 Open-label W8 W12

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Presentation on theme: "Design Randomisation* 1 : 1 Open-label W8 W12"— Presentation transcript:

1 POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6
Design Randomisation* 1 : 1 Open-label W8 W12 > 18 years Chronic HCV infection Genotype 1, 2, 3, 4, 5 or 6 Treatment-naïve or IFN-experienced Compensated cirrhosis ** allowed (exclusion of genotype 3 with cirrhosis) N = 501 SOF/VEL/VOX 400/100/100 mg QD SVR12 SOF/VEL 400/100 mg QD SVR12 N = 440 ** Metavir F4 or Ishak 5-6 or Fibroscan > 12.5 kPa or Fibrotest  > APRI > 2 * 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 Objective SVR12 (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 Jacobson IM. Gastroenterology 2017; 153:113-22

2 Baseline characteristics and patient disposition
POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6 Baseline characteristics and patient disposition SOF/VEL/VOX 8 weeks N = 501 SOF/VEL 12 weeks N = 440 Age, years, mean 53 55 Female, % 49 46 White / Black, % 78 / 10 83 / 11 Genotype, % 1a 1b 1 other 2 3 4 5 / 6 / unknown 34 13 < 4 / 6 / < 1 39 13 < 1 12 20 13 0 / 2 / 0 HCV RNA, log10 IU/mL, mean 6.1 6.2 IL28B CC, % 33 31 Cirrhosis, % 18 19 IFN-experienced, % 24 23 Discontinuation, N Adverse event / lost to follow-up / pregnancy 1 0 / 0 / 1 2 / 1 / 0 POLARIS-2 Jacobson IM. Gastroenterology 2017; 153:113-22

3 SVR12 overall and in genotype 1, %
POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6 SVR12 overall and in genotype 1, % SOF/VEL/VOX 8 weeks SOF/VEL 12 weeks % 100 98 98 99 97 97 95 * 93 92 80 21 relapses 4 lost to follow-up 16 relapses 14 relapses 2 relapses 60 40 3 relapses 1 discontinuation for AE 4 lost to follow-up 2 relapses 2 lost to follow-up 1 relapse 1 lost to follow-up 1 relapse 1 lost to follow-up 20 N= 501 440 233 232 169 172 63 59 Overall Genotype 1 Genotype 1a Genotype 1b * Difference (2-sided 95% CI) : -3.4 % (-6.2% to -0.6%)  non inferiority not met POLARIS-2 Jacobson IM. Gastroenterology 2017; 153:113-22

4 POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6
SVR12 in genotype 2 to 6, % SOF/VEL/VOX 8 weeks SOF/VEL 12 weeks % 100 100 100 100 100 99 98 97 97 94 92 80 2 relapses 3 lost to follow-up 2 relapses 1 relapse 60 1 lost to follow-up 40 1 discontinuation for AE 2 lost to follow-up 1 relapse 20 N= 63 53 92 89 63 57 18 30 9 2 Genotype 2 Genotype 3 Genotype 4 Genotype 5 Genotype 6 Unknown POLARIS-2 Jacobson IM. Gastroenterology 2017; 153:113-22

5 SVR12 by cirrhosis status, %
POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6 SVR12 by cirrhosis status, % SOF/VEL/VOX 8 weeks SOF/VEL 12 weeks % 100 98 99 96 91 80 60 14 relapses 3 LTFU 2 relapses 4 LTFU 1 DC due to AE 7 relapses 1 LTFU 1 relapse 40 20 411 356 90 84 N= No Cirrhosis N = 767 Cirrhosis N = 174 POLARIS-2 Jacobson IM. AASLD 2016, Abs. LB-12 ; Jacobson IM. Gastroenterology 2017; 153:113-22

6 POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6
SVR12 by baseline RASs, % SOF/VEL/VOX 8 weeks SOF/VEL 12 weeks % 100 99 99 100 99 100 100 98 94 91 95 80 60 40 20 N= 228 250 110 120 19 208 218 97 921 30 No RASs Any RASs NS3 only NS5A only NS3 + NS5A No RASs Any RASs NS3 only NS5A only NS3 + NS5A All 64 patients with baseline NS5B nucleoside inhibitor RASs achieved SVR12 * RASs were analyzed using a 15% cut off POLARIS-2 Jacobson IM. Gastroenterology 2017; 153:113-22

7 Impact of baseline NS5A RAS
POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6 Impact of baseline NS5A RAS For patients with genotype 1a, SVR12 with SOF/VEL/VOX 8 weeks 89% if baseline RASs 95% if no baseline RASs 88% if baseline Q80K 94% if absence of baseline 80K Viral resistance testing at failure Of 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 Jacobson IM. Gastroenterology 2017; 153:113-22

8 POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6
Adverse events SOF/VEL/VOX 8 weeks N = 501 SOF/VEL 12 weeks N = 440 At least one adverse event, % 72 69 Serious adverse events, N (%) related to study drug 15 (3%) 7 (2%) Grade 3-4 adverse events, N (%) 11 (2%) 6 (1%) Discontinuation due to adverse event, N (%) 2 (< 1%) * Death Adverse events in > 5% of patients, % Headache 27 23 Fatigue 21 20 Diarrhea 18 7 Nausea 16 9 Asthenia 6 Insomnia 5 Arthralgia 4 Grade 3-4 laboratory abnormalities, % Hemoglobin < 10 g/dl ALT > 5 x ULN / AST > 5 x ULN 1 0 / < 1 < 1 / 0 *1 upper respiratory tract infection and 1 Clostridium difficile infection, both not related to the study medication POLARIS-2 Jacobson IM. Gastroenterology 2017; 153:113-22

9 POLARIS-2 study: SOF/VEL/VOX 8 weeks vs SOF/VEL 12 weeks in patients with genotype 1 to 6
Summary SOF/VEL/VOX for 8 weeks resulted in a 95% SVR12 rate in DAA-naïve genotype 1-6 patients with and without cirrhosis Did not meet non-inferiority as compared to the 98% SVR12 rate with SOF/VEL for 12 weeks The difference between the regimens was largely attributed to more relapses among patients with genotype 1a infection in the SOF/VEL/VOX group SOF/VEL/VOX and SOF/VEL were safe and well tolerated Mild gastrointestinal adverse events (nausea and diarrhea) were associated with treatment regimens that included VOX There was no evidence of VOX-related hepatotoxicity These findings in DAA-naïve patients with or without cirrhosis underscore the very high rates of SVR conferred by SOF/VEL across all HCV genotypes SOF/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 Jacobson IM. AASLD 2016, Abs. LB-12 ; Jacobson IM. Gastroenterology 2017; 153:113-22

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