W12 N = 126 C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection Randomisation * 1:1  Design  Treatment regimens –Co-formulated.

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Presentation transcript:

W12 N = 126 C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection Randomisation * 1:1  Design  Treatment regimens –Co-formulated GZR/EBR 100/50 mg qd –SOF 400 mg qd : PEG-IFN  -2b: 1.5  g/kg every week, weight-based RBV (1000 or 1200 mg/day)  Objective –SVR 12 (HCV RNA < 15 IU/ml), with 2 sided 95% confidence interval, non-inferiority margin – 10%, superiority if lower margin greater than 0 –Treatment-emergent adverse events years HCV genotype 1 or 4 HCV RNA > IU/ml Naïve or pre-treated with PEG-IFN + RBV Compensated cirrhosis allowed No HBV or HIV co-infection SOF + PEG-IFN + RBV C-EDGE HEAD-TO-HEAD N = 129 GZR/EBR SVR 12 * Randomisation was stratified on genotype (1a vs non-1a) and cirrhosis (presence or absence) Sperl J. J Hepatology 2016, Aug 16 (Epub ahead of print)

GZR/EBR n = 129 SOF + PEG-IFN + RBV n = 126 Age, mean (years) Female, % White race, %99.2 Il28B CC, % Baseline HCV RNA, % > IU/ml > IU/ml Genotype : 1a / 1b / 4, %14.0 / 81.4 / / 82.5 / 4.0 Cirrhosis, % HCV treatment naïve PEG-IFN + RBV null response PEG-IFN + RBV partial response PEG-IFN + RBV relapse C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection Baseline characteristics C-EDGE HEAD-TO-HEAD Sperl J. J Hepatology 2016, Aug 16 (Epub ahead of print)

SVR 12 rates overall and by genotype Virologic failure Lost to follow-up/ discontinuation Genotype All genotypesGenotype 1a % * Estimated adjusted difference : 8.8 % (95% CI : 3.6% ; 15.3%) Genotype 1b GZR/EBRSOF + PEG-IFN + RBV  GZR/EBR is non-inferior and superior C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection C-EDGE HEAD-TO-HEAD Sperl J. J Hepatology 2016, Aug 16 (Epub ahead of print)

Resistance associated variants : prevalence in GZR/EBR group Detectable RAVs at baseline NS3 RAVs Genotype 1a10/18 (56%) : V36M (n=1), V55A (n=1), Q80K (n=2), V107I (n=1), S122G (n=3), I170V (n=2) Genotype 1b11/103 (11%) : V36L (n=1), V36I (n=1), T54S (n=5), V55A (n=1), V55I (n=2), Q80K (n=1), S122G (n=2), M175L (n=1) Genotype 4a0/1 Genotype 4d1/5 (20%) : V107I (n=1) NS5A RAVs Genotype 1a2/18 (11%) : M28V (n=2) Genotype 1b12/102 (12%) : Q30K (n=2), L31M (n=3), Y93H (n=7) Genotype 4a0/1 Genotype 4d1/5 (20%) : P58T (n=1) 100% of patients achieved SVR 12 with GZR/EBR, irrespective of presence or absence of baseline NS3 or NS5A RAVs C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection Sperl J. J Hepatology 2016, Aug 16 (Epub ahead of print)

GZR/EBR N = 129 SOF + PEG-IFN + RBV N = 126 p Any treatment-emergent adverse event, % < Any treatment-related adverse event, % < Serious adverse event, %0.84ns Serious drug related adverse event, % Discontinuation due to drug-related adverse event, %00.8ns Neutrophil count < 0.75 x 10 9 /l, % < Hemoglobin < 10 g/dl, % < Severe depression causing discontinuation, %00- Hepatic event causing discontinuation, %00- Treatment-emergent adverse events C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection C-EDGE HEAD-TO-HEAD Sperl J. J Hepatology 2016, Aug 16 (Epub ahead of print)

 Summary –12 weeks of GZR/EBR has superior efficacy to SOF + PEG-IFN + RBV on genotype 1 and genotype 4-infected patients High SVR 12 in all subpopulations –Experienced patients including PEG-IFN + RBV null responders (100%) –Cirrhosis (100%) –High baseline viral load (98.9%) –Superior safety profile of GZR/EBR No serious drug-related adverse events No discontinuations due to drug-related adverse events Superior hematological safety profile No hepatic safety events C-EDGE HEAD-TO-HEAD Study: GZR/EBR vs SOF + PEF-IFN + RBV in genotype 1 or 4 infection C-EDGE HEAD-TO-HEAD Sperl J. J Hepatology 2016, Aug 16 (Epub ahead of print)