Design W12 Open-label Liver transplant recipients

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Presentation transcript:

Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 Design W12 Open-label Liver transplant recipients Recurrent HCV infection after transplantation Treatment-naïve or experienced Genotype 1-6 Without cirrhosis or with compensated cirrhosis * N = 79 SOF/VEL SVR12 * Cirrhosis : Fibrotest® >0.75 + APRI >2 or Fibroscan® >12.5 kPa or liver biopsy SOF/VEL: 400/100 mg 1 tablet QD Objective SVR12 (HCV RNA < 15 IU/mL) SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7 1

Baseline characteristics Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 Baseline characteristics SOF/VEL 12W, N = 79 Mean age, years 62 Female, % 19 Race : White / Asian % 82 / 15 Mean BMI, kg/m² 28 Genotype 1a / 1b / 2 / 3 / 4, n 15 / 22 / 3 / 35 / 4 Mean years since transplantation (range) 8.7 (0.3-23.9) Fibrosis by Fibrotest®, n : F0-F1 / F2 / F3 / F4 / missing 10 / 35 / 11 / 21 / 2 Treatment-experienced, % IFN-based / DAA ± PEG-IFN +RBV 60 91 / 9 Immunosuppression use, % Tacrolimus Cyclosporine Sirolimus Everolimus Mycophenolate Azathioprine Prednisolone 71 14 10 6 24 11 1 SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7 2

Primary Endpoint (SVR12) Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 Primary Endpoint (SVR12) 37 96 95 100 80 60 40 20 % Total 93 97 15 ** 22 * 3 35 ** 4 79 Genotype 1 GT1a GT1b Genotype 2 Genotype 3 Genotype 4 * 1 patient stopped treatment after 7 days for hyperglycemia (GT1b) ** 2 patients relapsed after treatment cessation (GT1a and GT3) SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7

SVR12 by fibrosis stage (Fibrotest®) Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 SVR12 by fibrosis stage (Fibrotest®) 100 80 60 40 20 94 95 10 35 11 21 F4 % F3 F2 F0-F1 2 patients had missing Fibrotest® scores SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7

Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 RAS and SVR12 Baseline RAS N SVR12 NS5A 24/79 (30%) 22/24 (92%) NS5B 6/77 (8%) 6/6 (100%) Y93H 4 4/4 (100%) The 2 virological relapses occurred in patients with baseline NS5A RAS: GT3b-infected patient with A30K+L31M at baseline GT1a-infected patient with K24R at baseline SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7 5

Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 Adverse events and laboratory abnormalities, % SOF/VEL 12W N = 79 Any adverse event 78 Serious adverse event * 4 (n = 3 *) Adverse events in ≥ 10% of patients Headache Fatigue Cough 24 20 10 Adverse event leading to discontinuation 1 (n = 1 **) Acute rejection / Death 0 / 0 Grade 3 laboratory abnormalities Hyperglycemia Hyperuricemia Proteinuria 4 5 1 Grade 4 laboratory abnormalities Lymphopenia * Joint swelling, pneumonia and hepatocellular carcinoma, all unrelated to treatment ** Hyperglycemia (treatment-related) SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7 6

Sofosbuvir/velpatasvir for 12 weeks in liver transplant recipients with genotype 1-4 Summary 12 weeks of SOF/VEL achieved high cure rate (SVR12 of 96%) in liver transplantation recipients with relapse of HCV infection with genotypes 1-4 Good safety profile No rejection episode SOF/VEL Transplant Agarwal K. J Hepatol. 2018;69:603-7 7