SOLAR-2 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in...

SOLAR-2

LDV/SOF + RBV

Randomisation of the 7 groups

1 : 1Open-label

SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype 1 or 4

Design W12 W24

≥ 18yearsChronic HCV infection

Genotypes 1 or 4Treatment-naïve or

experiencedNo hepatocellular carcinoma

No prior exposure to NS5A inhibitor

No HBV or HIV co-infection

Manns M. EASL 2015. 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

Fibrosingcholestasic

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


Baseline characteristics, median or %

SOLAR-2 Manns M. EASL 2015. Abs. GO2 ; Forns X. EASL 2015;Abs. P0779

Post-transplantationF0-F3 + Child-Pugh A

Pre/post-transplantationChild-Pugh B + C

12W, N = 86 24W, N = 82 12W, N = 78 24W, N = 82

Age, years 58 60 58 58

Female 20% 21% 29% 28%

Genotype1a1b4

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%

MELD > 15 0 0 28% 23%

Ascites / Encephalopathy 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


7 subjects who were transplanted and 3 subjects who did not meet inclusion criteria are excluded

0

20

40

60

80

100 9585

9888

F0-F3 and Child-Pugh A

Post-transplantation

72 68

Child-Pugh B and C

Pre and Post-transplantation

86 65

12 Weeks 24 Weeks

SVR12 (HCV RNA < 15 IU/ml), % (90% CI)


N

Genotype 1 Genotype 4

Pre- and Post-Transplant

0

20

40

60

80

10091

57

10086

F0-F3 +Child-Pugh A

7 7

Child-Pugh B + C

11 70

20

40

60

80

100 96 8898 89

65 6175 58

Post-Transplant

Pre- and Post-Transplant

Post-Transplant

F0-F3 +Child-Pugh A

Child-Pugh B + C

SVR12 (HCV RNA < 15 IU/ml), % (90% CI)


Fibrosing cholestatic hepatitis

– Patients transplanted 0.2 to 1.6 years before

– All 11 (7 with 12W and 4 with 24W) achieved SVR12

Relapse 1 0 4 2 0 0 3 0

Death 2 1 4 4 1 0 0 1


12 Weeks 24 Weeks

0

20

40

60

80

100 87 8596

72

Child-Pugh C

23 20 18

Child-Pugh B

23

SVR12 (HCV RNA < 15 IU/ml) in Genotype 1, % (90% CI)

Child-Pugh CChild-Pugh B

% %Pre-transplant Post-transplant

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

20 2 416

12 Weeks 24 Weeks

N N

40

60

100

80

95

0

20

100 50 75

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) 0 0 20 (48)

Not assessed 3 12 12-10

-8

-6

-4

-2

0

2

4

N = 95

(-17)(-11)

(8)

N = 22

N = 18

Liver function change from baseline to follow-up W4

*Missing follow-up: N = 24




Post-transplant Pre/Post-transplantFibrosing

cholestatichepatitisF0–F3 + Child-Pugh A Child-Pugh B + C

12WN = 86

24WN = 82

12WN = 78

24 WN = 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

Death 2 (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 (%)


No deaths were considered treatment related


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 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in...

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