A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks Compared to Sofosbuvir/Velpatasvir for 1 Weeks in DAA-Naïve Genotype 1 6 HCV Infected Patients: The POLARIS- Study Ira M. Jacobson, Tarik Asselah, Ronald Nahass, Bal R. Bhandari, Albert Tran, Robert H. Hyland, Luisa M. Stamm, Hadas Dvory-Sobol, Yanni Zhu, Diana M. Brainard, G. Mani Subramanian, John G. McHutchison, Stephen Shafran, Mitchell Davis, Catherine A. Stedman, Eric Lawitz, Edward J. Gane Abstract LB-1 POLARIS-: Pangenotypic Single Tablet Regimen with Inhibitors of HCV NS5B (Nucleotide) + + NS3 Sofosbuvir (SOF)/Velpatasvir (VEL) SOF Nucleotide polymerase SOF: Nucleoside polymerase with activity against HCV GT 1-6 VEL VEL: Potent pangenotypic VOX NS3/4A protease SOF Nucleotide polymerase VEL VOX NS3/4A protease Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 194. Voxilaprevir (VOX) HCV NS3/4A Pl with potent antiviral activity against GT 1-6, including most Once daily, oral, fixed-dose combination (4// mg) for GT 1-6
POLARIS-: Study Design Week 8 1 4 n=51 n=44 SVR1 SVR1 Open-label, randomized, active-comparator trial at 117 sites (USA, Canada, France, Germany, UK, Australia, and New Zealand) Genotypes 1 6 with and without compensated cirrhosis GT 3 patients with cirrhosis were enrolled in a separate study (POLARIS-3) 1:1 randomization for GT 1 4 (other GTs assigned to ) Stratified by GT, cirrhosis, and prior treatment experience (naïve or IFN experienced) Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 194. POLARIS-: Randomized Controlled Trial of for 8 Weeks versus for 1 Weeks Open-label Treatment-naïve and experienced (interferon/ribavirin only) HCV genotype 1,, 3, 4, 5, 6 Jacobson I, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. LB-1. 8 Weeks n=51 1 Weeks n=44 Mean age, y (range) 53 (18 78) 5 (19 8) Male, n (%) 55 (51) 37 (54) White, n (%) 391 (78) 365 (83) Mean BMI, kg/m (range) 7 (17 57) 7 (18 54) Cirrhosis, n (%) 9 (18) 84 (19) 1a / 1b / Other 169 (34) / 63 (13) / 1 (<1) 17 (39) / 59 (13) / 1 (<1) 63 (13) 53 (1) Genotype, n (%)* 3 9 (18) 89 () 4 63 (13) 57 (13) 5 / 6 / Unknown 18 (4) / 3 (6) / (<1) / 9 () / IFN experienced, n (%) 118 (4) (31) IL8B CC, n (%) 166 (33) 136 (31) Mean HCV RNA, log 1 IU/mL (range) 6.1 (.7 7.6) 6. (4. 7.6)
POLARIS-: Results (SVR1) 95 98 8 6 4 s 3 relapses 1 DC due to AE 476/51 43/44 8 Weeks 1 Weeks Jacobson I, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. LB-1. POLARIS-: Results - SVR1 by Genotype (GT 1) 95 8 weeks, n=51 1 weeks, n=44 98 98 99 93 9 8 6 4 s 16 relapses 14 relapses relapses 3 relapses 1 AEDC relapse LTFU 476 51 43 44 17 33 8 3 Overall GT 1 GT 1a GT 1b 155 169 17 17 61 63 57 59 AEDC, Discontinuation due to AE. Error bars represent 95% confidence intervals. of patients (%) with GT 1 Other achieved SVR1 (1 each in the and groups). Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 194.
POLARIS-: Results - SVR1 by Genotype (GT 6) 8 weeks, n=51 1 weeks, n=44 99 98 9 94 8 6 4 relapses relapses 3 LTFU 1AEDC LTFU 61 63 53 53 91 9 86 89 58 63 56 57 GT GT 3 GT 4 GT 5 GT 6 Unknown 17 18 3 3 9 9 AEDC, Discontinuation due to AE. Error bars represent 95% confidence intervals. Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 194. POLARIS-: Results - SVR1 by Cirrhosis Status No Cirrhosis n=767 96 98 91 Cirrhosis n=174 99 8 8 6 6 4 14 relapses 3 LTFU relapses 1 DC due to AE 4 7 relapses 394/411 8 weeks 349/356 1 weeks 8/9 8 weeks 83/84 1 weeks Error bars represent 95% confidence intervals. Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 194.
POLARIS-: Results - SVR1 by Baseline n=44 n=51 93 91 94 6 4 99 98 6 11 17 9 9 3 31 No Any NS3 NS3 + 8 8 98 3 3 34 51 11 114 11 No Any NS3 NS3 + 6 4 All 64 patients with baseline NS5B nucleoside achieved SVR1 patients in the group and 9 patients in the group were excluded due to incomplete RAS data; were analyzed using a 15% cut off; error bars represent 95% confidence intervals. Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 194. A Randomized, Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks and Sofosbuvir/Velpatasvir for 1 Weeks for Patients with Genotype 3 HCV Infection and Cirrhosis: The POLARIS-3 Study Graham R. Foster, Alexander Thompson, Peter J. Ruane, Sergio Borgia, Gregory Dore, Kimberly Workowski, Robert H. Hyland, Jing Wang, Evguenia S. Svarovskaia, Luisa M. Stamm, Diana M. Brainard, G. Mani Subramanian, John G. McHutchison, Thomas Berg, Kosh Agarwal, Brian Conway, Jordan Feld, Bernard Willems, Stuart K. Roberts, Eric Gane Abstract 58
POLARIS-3: Study Design Week 8 1 4 n=11 n=19 SVR1 SVR1 Open-label, randomized, active-comparator trial conducted at 84 sites (USA, Canada, France, Germany, UK, Australia, New Zealand) Patients with GT 3, all of whom had cirrhosis 1:1 randomization Stratified by prior treatment experience (IFN experienced or naïve) Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 58. POLARIS-3: Randomized Controlled Trial of for 8 Weeks Versus for 1 Weeks in Patients with HCV Genotype 3 and Cirrhosis 8 Weeks n=11 1 Weeks n=19 Mean Age, y (range) 54 (5 75) 55 (31 69) Male, n (%) 74 (67) 83 (76) White, n (%) (91) (89) Mean BMI, kg/m (range) 8 ( 5) 7 (18 46) Mean Platelets, x1 3 /µl (range) 14 (37 351) 15 (51 9) IFN Experienced, n (%) 35 (3) 3 (9) IL8B CC, n (%) 41 (37) 5 (48) Mean HCV RNA, log 1 IU/mL (range) 6. (1.6 7.6) 6.3 (4.1 7.5) Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 58.
POLARIS-3: Results (SVR1) 96 96 8 6 4 relapses 1 withdraw consent 1 death 1 breakthrough 1 discontinued due to AE 16/11 8 Weeks 15/19 1 Weeks There were 6 patients with Y93H in the group and 4 in the group; all achieved SVR1 No treatment emergent in the group. In the group, both virologic failures had Y93H Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 58. POLARIS-3: Results - SVR1 by Prior Treatment Treatment Naive n=15 Treatment Experienced n=67 96 99 91 8 8 6 4 6 4 7/75 76/77 34/35 9/3 Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 58.
POLARIS-3: Results - SVR1 by Baseline n=19 n=11 95 6 4 3 3 Any 4 4 NS3 8 8 95 8 84 No 3 3 Any NS3 1 1 NS3 + 6 4 76 8 No 19 17 NS3 + There were 6 patients with Y93H in the group and 4 in the group; all achieved SVR1 No treatment emergent in the group; in the group, both virologic failures had Y93H 3 patients in the group and 6 patients in the group were excluded due to incomplete RAS data; were analyzed using a 15% cut off; error bars represent 95% confidence intervals. Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 16; Abst. 58.