SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
Randomisation
of the 7 groups
1:1
Open-label
 Design
≥ 18years
Chronic HCV infection
Genotypes 1 or 4
Treatment-naïve or
experienced
No hepatocellular carcinoma
No prior exposure
to NS5A inhibitor
No HBV or HIV co-infection
LDV/SOF 90mg/400 mg : 1 pill qd
RBV : 1000 or 1200 mg/day (bid
dosing) according to body weight
(< or ≥ 75 kg) ; 600 mg/day with
dose escalation in Child-Pugh B/C
SOLAR-2
Pretransplantation
N = 107
W12
W24
Child-Pugh B
Child-Pugh C
No cirrhosis
LDV/SOF + RBV
Chid-Pugh A
Child-Pugh B
PostTransplantation
N = 221
LDV/SOF + RBV
Child-Pugh C
Fibrosing
cholestasic
hepatitis
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
Baseline characteristics, median or %
Post-transplantation
F0-F3 + Child-Pugh A
Pre/post-transplantation
Child-Pugh B + C
12W, N = 86
24W, N = 82
12W, N = 78
24W, N = 82
58
60
58
58
Female
20%
21%
29%
28%
Genotype
1a
1b
4
48%
40%
13%
51%
37%
12%
49%
42%
9%
46%
43%
11%
HCV RNA, log10 IU/ml
6.5
6.5
6.0
5.9
Previous HCV therapy
84%
79%
74%
80%
0
0
28%
23%
3% / 0
2% / 0
65% / 47%
78% / 55%
Albumin, g/dl
4.0
3.9
2.8
2.9
Creatinine clearance, ml/min
62
65
79
80
Age, years
MELD > 15
Ascites / Encephalopathy
SOLAR-2
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
SVR12 (HCV RNA < 15 IU/ml), % (90% CI)
12 Weeks
95
100
24 Weeks
98
85
88
80
60
40
20
0
N
86
65
72
F0-F3 and Child-Pugh A
Post-transplantation
68
Child-Pugh B and C
Pre and Post-transplantation
 7 subjects who were transplanted and 3 subjects who did not meet inclusion
criteria are excluded
SOLAR-2
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
SVR12 (HCV RNA < 15 IU/ml), % (90% CI)
12 Weeks
24 Weeks
Genotype 1
100
96
98
Genotype 4
88
89
100
91
100
86
57
80
80
60
60
40
40
20
20
0
75
58
F0-F3 +
Child-Pugh A
PostTransplant
65
61
Child-Pugh
B+C
Pre- and
Post-Transplant
0
– Patients
transplanted 0.2 to
1.6 years before
– All 11 (7 with 12W
and 4 with 24W)
achieved SVR12
11
7
7
F0-F3 +
Child-Pugh A
7
Child-Pugh
B+C
PostPre- and
Transplant Post-Transplant
Relapse
1
0
4
2
0
0
3
0
Death
2
1
4
4
1
0
0
1
SOLAR-2
 Fibrosing
cholestatic hepatitis
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
SVR12 (HCV RNA < 15 IU/ml) in Genotype 1, % (90% CI)
12 Weeks
24 Weeks
Pre-transplant
%
87
100
96
85
%
72
100
80
80
60
60
40
40
20
20
0
N
23
23
Child-Pugh B
20
Post-transplant
18
Child-Pugh C
0
N
95
100
50
75
20
16
2
4
Child-Pugh B
Child-Pugh C
Relapse
3
1
1
1
0
0
0
0
Death
0
0
1
3
1
0
1
1
 7 subjects who were transplanted and 3 subjects who did not meet inclusion
criteria are excluded
SOLAR-2
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
Liver function change from baseline to follow-up W4
Change in Child-Pugh Class, n (%)
MELD Score Change
Pre/Post-Transplant (Child-Pugh B and C, N = 136*)
Baseline Child-Pugh
(8)
4
2
N = 95
A (5–6) B (7–9)
N =73 N =100
N = 18
0
N = 22
-2
-4
-6
-8
-10
(-11)
(-17)
Followup W4
ChildPugh
C (10–12)
N =54
A (5–6)
67
(96)
31
(35)
2 (5)
B (7–9)
3 (4)
57
(65)
20 (48)
C (10–12)
0
0
20 (48)
Not
assessed
3
12
12
*Missing follow-up: N = 24
SOLAR-2
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
Adverse events, n (%)
Post-transplant
Pre/Post-transplant
F0–F3 + Child-Pugh A
Child-Pugh B + C
Fibrosing
cholestatic
hepatitis
12W
N = 86
24W
N = 82
12W
N = 78
24 W
N = 82
N = 11
Adverse event
79 (92)
78 (95)
74 (95)
77 (94)
11 (100)
Grade 3‒4 adverse event
16 (19)
20 (24)
15 (19)
25 (30)
2 (18)
Serious adverse event
12 (14)
12 (15)
22 (28)
23 (28)
5 (45%)
Treatment-related SAEs*
0
3 (4)
2 (3)
4 (5)
1 (9)
Treatment discontinuation due to AE†
0
1 (1)
1 (1)
4 (5)
0
2 (2)
1 (1)
3 (4)
4 (5)
0
Death
*Fall, anemia (5), vomiting, diarrhea, dyspnea, hyperbilirubinemia
†edema,
dehydration, HCC (2), type 2 diabetes mellitus, hyperbilirubinemia
No deaths were considered treatment related
SOLAR-2
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779
SOLAR-2 Study: LDV/SOF + RBV in decompensated
and post-liver transplant with genotype 1 or 4
 Summary
– LDV/SOF + RBV resulted in high SVR12 rates in HCV patients
with advanced liver disease, irrespective of transplantation status
• For genotype 1, SVR12 were similar between 12 and 24 weeks
– Among patients with cirrhosis, virologic response was associated
with improvements in MELD and Child-Pugh scores largely due to
decreases in bilirubin and improvement in synthetic function
(e.g. albumin)
– LDV/SOF + RBV for 12-24 weeks was generally safe and well
tolerated in patients with advanced liver disease, pre and post
liver transplantation
– Limitations
• Few genotype 4
SOLAR-2
Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779