SOLAR-2 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype.

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Presentation transcript:

SOLAR-2 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype 1 or 4  Design W12W24 ≥ 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 Manns M. EASL Abs. GO2 ; Forns X. EASL 2015;Abs. P0779 Child-Pugh B LDV/SOF + RBV Child-Pugh C No cirrhosis Child-Pugh B Chid-Pugh A Child-Pugh C Fibrosing cholestasic hepatitis 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 Pre- transplantation N = 107 Post- Transplantation N = 221

SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype 1 or 4 Baseline characteristics, median or % SOLAR-2 Manns M. EASL Abs. GO2 ; Forns X. EASL 2015;Abs. P0779 Post-transplantation F0-F3 + Child-Pugh A Pre/post-transplantation Child-Pugh B + C 12W, N = 8624W, N = 8212W, N = 7824W, N = 82 Age, years Female20%21%29%28% Genotype 1a 1b 4 48% 40% 13% 51% 37% 12% 49% 42% 9% 46% 43% 11% HCV RNA, log 10 IU/ml Previous HCV therapy84%79%74%80% MELD > %23% Ascites / Encephalopathy3% / 02% / 065% / 47%78% / 55% Albumin, g/dl Creatinine clearance, ml/min

SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype 1 or 4  7 subjects who were transplanted and 3 subjects who did not meet inclusion criteria are excluded F0-F3 and Child-Pugh A Post-transplantation 7268 Child-Pugh B and C Pre and Post-transplantation Weeks24 Weeks SVR 12 (HCV RNA < 15 IU/ml), % (90% CI) SOLAR-2 Manns M. EASL Abs. GO2 ; Forns X. EASL 2015;Abs. P0779 N

Genotype 1Genotype 4 Pre- and Post-Transplant F0-F3 + Child-Pugh A 77 Child-Pugh B + C Post- Transplant Pre- and Post-Transplant F0-F3 + Child-Pugh A Child-Pugh B + C SVR 12 (HCV RNA < 15 IU/ml), % (90% CI) SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype 1 or 4  Fibrosing cholestatic hepatitis –Patients transplanted 0.2 to 1.6 years before –All 11 (7 with 12W and 4 with 24W) achieved SVR 12 Relapse Death SOLAR-2 Manns M. EASL Abs. GO2 ; Forns X. EASL 2015;Abs. P Weeks24 Weeks

Child-Pugh C Child-Pugh B 23 SVR 12 (HCV RNA < 15 IU/ml) in Genotype 1, % (90% CI) Child-Pugh CChild-Pugh B % % Pre-transplantPost-transplant Relapse Death SOLAR-2 Manns M. EASL 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  7 subjects who were transplanted and 3 subjects who did not meet inclusion criteria are excluded Weeks24 Weeks NN

MELD Score Change Change in Child-Pugh Class, n (%) Pre/Post-Transplant (Child-Pugh B and C, N = 136*) Baseline Child-Pugh A (5–6) N =73 B (7–9) N =100 C (10–12) N =54 Follow- up W4 Child- Pugh A (5–6) 67 (96) 31 (35) 2 (5) B (7–9) 3 (4) 57 (65) 20 (48) C (10–12) 0020 (48) Not assessed 312 N = 95 (-17) (-11) (8) N = 22 N = 18 Liver function change from baseline to follow-up W4 *Missing follow-up: N = 24 SOLAR-2 Manns M. EASL 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

Post-transplantPre/Post-transplant Fibrosing cholestatic hepatitis F0–F3 + Child-Pugh AChild-Pugh B + C 12W N = 86 24W N = 82 12W N = W N = 82 N = 11 Adverse event79 (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 event12 (14)12 (15)22 (28)23 (28)5 (45%) Treatment-related SAEs*03 (4)2 (3)4 (5)1 (9) Treatment discontinuation due to AE † 01 (1) 4 (5)0 Death2 (2)1 (1)3 (4)4 (5)0 *Fall, anemia (5), vomiting, diarrhea, dyspnea, hyperbilirubinemia † edema, dehydration, HCC (2), type 2 diabetes mellitus, hyperbilirubinemia Adverse events, n (%) SOLAR-2 Manns M. EASL Abs. GO2 ; Forns X. EASL 2015;Abs. P0779 No deaths were considered treatment related

SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype 1 or 4  Summary –LDV/SOF + RBV resulted in high SVR 12 rates in HCV patients with advanced liver disease, irrespective of transplantation status For genotype 1, SVR 12 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 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 Abs. GO2 ; Forns X. EASL 2015;Abs. P0779