A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir ...•1:1 randomization for GT 1–4 (other GTs...
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A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks Compared to Sofosbuvir/Velpatasvir for 12 Weeks in DAA-Naïve Genotype 1–6 HCV Infected Patients: The POLARIS-2 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-12 POLARIS-2: Pangenotypic Single Tablet Regimen with Inhibitors of HCV NS5B (Nucleotide) + NS5A + NS3 Sofosbuvir (SOF)/Velpatasvir (VEL) • SOF: Nucleoside polymerase inhibitor with activity against HCV GT 1-6 • VEL: Potent pangenotypic NS5A inhibitor Voxilaprevir (VOX) • HCV NS3/4A Pl with potent antiviral activity against GT 1-6, including most RASs SOF/VEL/VOX • Once daily, oral, fixed-dose combination (400/100/100 mg) for GT 1-6 Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194. VEL NS5A inhibitor SOF Nucleotide polymerase inhibitor VOX NS3/4A protease inhibitor VEL NS5A inhibitor SOF Nucleotide polymerase inhibitor VOX NS3/4A protease inhibitor
Transcript of A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir ...•1:1 randomization for GT 1–4 (other GTs...
A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks Compared
to Sofosbuvir/Velpatasvir for 12 Weeks in DAA-Naïve Genotype 1–6 HCV Infected Patients: The POLARIS-2 StudyIra 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-12
POLARIS-2: Pangenotypic Single Tablet Regimen with Inhibitors of HCV NS5B (Nucleotide) + NS5A + NS3
Sofosbuvir (SOF)/Velpatasvir (VEL)• SOF: Nucleoside polymerase inhibitor with activity
against HCV GT 1-6• VEL: Potent pangenotypic
NS5A inhibitor
Voxilaprevir (VOX)• HCV NS3/4A Pl with potent antiviral activity
against GT 1-6, including most RASs
SOF/VEL/VOX• Once daily, oral, fixed-dose combination
(400/100/100 mg) for GT 1-6
Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.
VELNS5Ainhibitor
SOFNucleotidepolymerase
inhibitor
VOXNS3/4Aproteaseinhibitor
VELNS5Ainhibitor
SOFNucleotidepolymerase
inhibitor
VOXNS3/4Aproteaseinhibitor
POLARIS-2: Study Design
• 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 SOF/VEL/VOX) • Stratified by GT, cirrhosis, and prior treatment experience (naïve or IFN experienced)
SOF/VEL/VOXn=501
SOF/VELn=440
0 8 12Week
SVR12
SVR12
20 24
Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.
POLARIS-2: Randomized Controlled Trial of SOF/VEL/VOX for 8 Weeks versus SOF/VEL for 12 Weeks • Open-label• Treatment-naïve and experienced (interferon/ribavirin only)• HCV genotype 1, 2, 3, 4, 5, 6
Jacobson I, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. LB-12.
SOF/VEL/VOX8 Weeks
n=501
SOF/VEL12 Weeks
n=440Mean age, y (range) 53 (18–78) 52 (19–82)Male, n (%) 255 (51) 237 (54)White, n (%) 391 (78) 365 (83)Mean BMI, kg/m2 (range) 27 (17–57) 27 (18–54)Cirrhosis, n (%) 90 (18) 84 (19)
Genotype, n (%)*
1a / 1b / Other 169 (34) / 63 (13) / 1 (<1) 172 (39) / 59 (13) / 1 (<1)2 63 (13) 53 (12)3 92 (18) 89 (20)4 63 (13) 57 (13)5 / 6 / Unknown 18 (4) / 30 (6) / 2 (<1) 0 / 9 (2) / 0
IFN experienced, n (%) 118 (24) 100 (31)IL28B CC, n (%) 166 (33) 136 (31)Mean HCV RNA, log10 IU/mL (range) 6.1 (2.7–7.6) 6.2 (4.0–7.6)
POLARIS-2: Results (SVR12)
Jacobson I, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. LB-12.
95 98
0
20
40
60
80
100
SOF/VEL/VOX 8 Weeks SOF/VEL 12 Weeks
476/501 432/440
21 relapses4 LTFU
3 relapses1 DC due to AE4 LTFU
SVR
12, %
POLARIS-2:Results - SVR12 by Genotype (GT 1)
AEDC, Discontinuation due to AE. Error bars represent 95% confidence intervals. 2 of 2 patients (100%) with GT 1 Other achieved SVR12 (1 each in the SOF/VEL/VOX and SOF/VEL groups).
SOF/VEL/VOX 8 weeks, n=501 SOF/VEL 12 weeks, n=440
95 93 929798 98 99 97
0
20
40
60
80
100
Overall GT 1a GT 1bGT 1
476501
155169
6163
432440
170172
5759
217233
228232
3 relapses1 AEDC4 LTFU
14 relapses
1 relapse1 LTFU
2 relapses
1 relapse1 LTFU
16 relapses
2 relapse2 LTFU
SVR
12, %
21 relapses4 LTFU
Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.
POLARIS-2:Results - SVR12 by Genotype (GT 2–6)
AEDC, Discontinuation due to AE. Error bars represent 95% confidence intervals.
SOF/VEL/VOX 8 weeks, n=501 SOF/VEL 12 weeks, n=440
97 99 92 94 100 100100 97 98
0
100
00
20
40
60
80
100
5657
5353
99
8689
GT 2 GT 3 GT 4 GT 5 GT 6 Unknown
2 relapses 1 relapse1 LTFU
1AEDC2 LTFU
2 relapses3 LTFU
1 relapse
1718
5863
6163
3030
9192
22
SVR
12, %
Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.
POLARIS-2:Results - SVR12 by Cirrhosis Status
Error bars represent 95% confidence intervals.
96 98
0
20
40
60
80
100
SOF/VEL/VOX8 weeks
SOF/VEL12 weeks
394/411
No Cirrhosisn=767
349/356
14 relapses3 LTFU
2 relapses4 LTFU
1 DC due to AE
SVR
12, %
91 99
0
20
40
60
80
100
SOF/VEL/VOX8 weeks
SOF/VEL12 weeks
83/8482/90
Cirrhosisn=174
7 relapses1 LTFU 1 relapse
Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.
POLARIS-2:Results - SVR12 by Baseline RASs
• All 64 patients with baseline NS5B nucleoside inhibitor RASs achieved SVR12
20 patients in the SOF/VEL/VOX group and 9 patients in the SOF/VEL group were excluded due to incomplete RAS data; RASs were analyzed using a 15% cut off; error bars represent 95% confidence intervals.
SOF/VEL/VOXn=501
SOF/VELn=440
NoRASs
AnyRASs
NS3Only
NS5AOnly
NS3 + NS5A
98 99 100 98 97
0
20
40
60
80
100
206211
217220
3031
9797
9092
97 93 91 94 100
0
20
40
60
80
100
223230
234251
2020
100110
114121
NoRASs
AnyRASs
NS3Only
NS5AOnly
NS3 + NS5A
SVR
12, %
SVR
12, %
Bourlière M, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 194.
A Randomized, Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevirfor 8 Weeks and Sofosbuvir/Velpatasvir for 12 Weeks for Patients with
Genotype 3 HCV Infection and Cirrhosis: The POLARIS-3 StudyGraham 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 258
POLARIS-3: Study Design
• 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)
SOF/VEL/VOXn=110
SOF/VELn=109
0 8 12Week
SVR12
SVR12
20 24
Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 258.
POLARIS-3: Randomized Controlled Trial of SOF/VEL/VOX for 8 Weeks Versus SOF/VEL for 12 Weeks in Patients with HCV Genotype 3 and Cirrhosis
Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 258.
SOF/VEL/VOX8 Weeks
n=110
SOF/VEL12 Weeks
n=109
Mean Age, y (range) 54 (25–75) 55 (31–69)
Male, n (%) 74 (67) 83 (76)
White, n (%) 100 (91) 97 (89)
Mean BMI, kg/m2 (range) 28 (20–50) 27 (18–46)
Mean Platelets, x103 /µL (range) 14 (37–351) 150 (51–292)
IFN Experienced, n (%) 35 (32) 32 (29)
IL28B CC, n (%) 41 (37) 52 (48)
Mean HCV RNA, log10 IU/mL (range) 6.0 (1.6–7.6) 6.3 (4.1–7.5)
POLARIS-3: Results (SVR12)
• There were 6 patients with Y93H in the SOF/VEL/VOX group and 4 in the SOF/VEL group; all achieved SVR12
• No treatment emergent RASs in the SOF/VEL/VOX group. In the SOF/VEL group, both virologic failures had Y93H
Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 258.
96 96
0
20
40
60
80
100
SOF/VEL/VOX 8 Weeks SOF/VEL 12 Weeks
106/110
2 relapses1 withdraw consent
1 death
105/109
1 breakthrough1 relapse
1 discontinued due to AE1 LTFU
SVR
12, %
POLARIS-3:Results - SVR12 by Prior Treatment
96 99
0
20
40
60
80
100
SOF/VEL/VOX SOF/VEL
Treatment Naiven=152
SVR
12, %
Treatment Experiencedn=67
97 91
0
20
40
60
80
100
SOF/VEL/VOX SOF/VEL
29/3272/75 34/3576/77
Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 258.
POLARIS-3:Results - SVR12 by Baseline RASs
• There were 6 patients with Y93H in the SOF/VEL/VOX group and 4 in the SOF/VEL group; all achieved SVR12
• No treatment emergent RASs in the SOF/VEL/VOX group; in the SOF/VEL group, both virologic failures had Y93H
3 patients in the SOF/VEL/VOX group and 6 patients in the SOF/VEL group were excluded due to incomplete RAS data; RASs were analyzed using a 15% cut off; error bars represent 95% confidence intervals.
SOF/VELn=109
NoRASs
AnyRASs
NS3Only
NS5AOnly
NS3 + NS5A
95100 100 100
00
20
40
60
80
100
7680
2323
44
1917
SOF/VEL/VOXn=110
95100 100 100 100
0
20
40
60
80
100
8084
2323
2020
NoRASs
AnyRASs
NS3Only
NS5AOnly
NS3 + NS5A
SVR
12, %
SVR
12, %
11
22
Foster G, et al. 67th AASLD; Boston, MA; November 11-15, 2016; Abst. 258.
