Open-label W24 ≥ 18 years Chronic HCV infection All genotypes HCV RNA ≥ 10,000 IU/ml Liver transplantation 6-150 months earlier Child Pugh ≤ 7 and MELD.

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VALENCE SOF + RBV Not randomised Open label* ≥ 18 years Chronic HCV infection Genotype 2 or 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve or prior IFN-based.

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Genotype 1 HCV infection Stable immunosuppressive therapy

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection

No cirrhosis or compensated cirrhosis** No HBV or HIV co-infection

Failure to achieve SVR on No HBV or HIV co-infection

QUARTZ II-III : OBV/PTV/r + SOF RBV in genotype 2 or 3

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ION-3 Study: LDV/SOF + RBV for naïve genotype 1

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LDV/SOF ± RBV in genotype 3 or 6 – Phase 2

SOF/VEL in liver transplantation with genotype 1-4 infection

Sequencing cohorts Open-label Design W8 W12 ≥ 18 years

Presentation transcript:

Open-label W24 ≥ 18 years Chronic HCV infection All genotypes HCV RNA ≥ 10,000 IU/ml Liver transplantation months earlier Child Pugh ≤ 7 and MELD ≤ 17 Steroids ≤ 5 mg/day No HBV or HIV coinfection –SOF 400 mg : 1 pill qd –RBV : 400mg/day escalating to 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg), dose adapted on hemoglobin level  Objective –Primary endpoint : SVR 12 (HCV RNA < 12 IU/ml) by intention to treat, with 2-sided 95% CI, no formal statistical criteria SOF + RBV SVR 12 N = 40 HCV RECURRENCE POST-TRANSPLANT Charlton M. Gastroenterology 2015;148:  Design HCV Recurrence Post-Transplant Study: SOF+ RBV for recurrent HCV infection after liver transplantation

N = 40 Median age, years59 Female22% Genotype 1a / 1b / 3 / 4, N22 / 11 / 6 / 1 IL28B CC genotype33% HCV RNA log 10 IU/ml, median6.74 Prior HCV treatment IFN or PEG-IFN only PEG-IFN + RBV PI + PEG-IFN + RBV Other + PEG-IFN + RBV 88% 9% 63% 26% 3% Response to last HCV regimen Breakthrough / Relapse / Partial / Non response / Unknown11% / 26% / 20% / 35% / 11% Metavir : F0-F2 / F3 / F437% / 23% / 40% Years since liver transplantation, median (range)4.3 (1.0 – 10.6) Child Pugh score : 5 / 6 / 760% / 30% / 10% SVR 12, N (% [90% CI])28 (70% [56-82]) Relapse, N (%)12 (30%) HCV RECURRENCE POST-TRANSPLANT Charlton M. Gastroenterology 2015;148: Baseline characteristics and outcome

HCV Recurrence Post-Transplant Study: SOF+ RBV for recurrent HCV infection after liver transplantation  SVR 12 according to subgroups –Rate lower if Male Cirrhosis Non-CC IL28B genotypes HCV Genotype 1b  Resistance assessment –NS5B sequencing : no baseline S282T variant –At relapse, 1 patient with emergence of V321A  Pharmacokinetic assessment –Increase in metabolite GS (< 2 fold) and SOF AUC tau in the post-transplant period  Safety –No deaths, graft losses or rejection –Grade 3 adverse events in 6 patients –Serious adverse events : 10 in 6 patients, all unrelated to study drugs –Adverse events leading to discontinuation : 1 pneumonia, 1 hepatocarcinoma HCV RECURRENCE POST-TRANSPLANT Charlton M. Gastroenterology 2015;148:108-17

HCV Recurrence Post-Transplant Study: SOF+ RBV for recurrent HCV infection after liver transplantation  Summary –In this open-label, uncontrolled, non randomised study, 24 weeks of SOF + RBV without interferon led to SVR 12 in 70% of patients (28 of 40) with recurrence of HCV infection after liver transplantation –This study confirms the absence of impact of SOF + RBV on co-administered immunosuppressive agents No net directional changes in trough levels of cyclosporine or tacrolimus were observed during the study HCV RECURRENCE POST-TRANSPLANT Charlton M. Gastroenterology 2015;148:108-17