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Design W12 W16 Randomisation Open-label ≥ 18 years HCV genotype 1 or 4

Published byHarvey Ferguson Modified over 6 years ago

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Presentation on theme: "Design W12 W16 Randomisation Open-label ≥ 18 years HCV genotype 1 or 4"— Presentation transcript:

1 MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen
Design W12 W16 Randomisation Open-label ≥ 18 years HCV genotype 1 or 4 HCV RNA ≥ IU/mL Failure to DAA regimen (maximum of 40% NS5A naïve) Without cirrhosis or compensated cirrhosis (maximum 50%) No HBV or HIV co-infection N = 44 GLE/PIB SVR12 GLE/PIB SVR12 N = 47 GLE/PIB: 100/40 mg 3 tablets QD Objective SVR12 (HCV RNA < 15 IU/ml), with 2-sides 95% CI, by ITT MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print) 1

2 Baseline characteristics
MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen Baseline characteristics 12 weeks N = 44 16 weeks N = 47 Median age, years 57 56 Female, % 30 Race: white / black , % 77 / 20 75 / 23 Genotype 1a / 1b / 1c / 4, % 80 / 18 / 0 / 2 71 / 23 / 2 / 6 Median HCV RNA, log10 IU/mL 6.1 6.3 Compensated cirrhosis, % 34 26 Previous DAA regimen, % NS3/4A only (NS5A-naïve) NS5A only NS3/4A + NS5A Prior DAA treatment response, % On-treatment failure Virologic relapse 32 68 28 72 Baseline NS3 RASs only, % Baseline NS5A RASs only, % Baseline NS3 + NS5A RASs, % 9 52 9 MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print) 2

3 SVR12 according to prior DAA class use, % (95% CI)
MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen SVR12 according to prior DAA class use, % (95% CI) GLE/PIB 12 weeks GLE/PIB 16 weeks 89 (76-95) 100 (79-100) 79 (52-92) 80 60 40 All patients PI only NS5A 20 44 14 16 % PI + NS5A 88 (64-97) 81 (57-93) 94 (74-99) 100 (77-100) 91 (80-97) 80 60 40 20 47 13 18 16 % All patients PI only NS5A PI + NS5A Breakthrough 1 Relapse 4 4 MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print) 3

4 SVR12 by NS3 and NS5A RASs at baseline, % (95% CI)
MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen SVR12 by NS3 and NS5A RASs at baseline, % (95% CI) GLE/PIB 12 weeks GLE/PIB 16 weeks 100 (77-100) 83 (64-93) 80 60 40 No RASs NS3 only 20 13 2 15 % NS5A 5 NS3 + 96 (79-99) 100 (77-100) 80 60 40 20 13 4 23 % No RASs NS3 only NS5A 25 NS3 + Breakthrough 1 Relapse 3 1 3 13 patients with baseline Y93H/N NS5A RASs: 13/13 achieved SVR12 MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print) 4

5 MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen
9 virologic failures : 4 relapses (R) and 5 virologic breakthroughs (B) GLE/PIB 12 weeks Prior DAA regimen(s) Genotype Type of failure NS3 RAVs NS5A RVAs Baseline Failure LDV/SOF 1a B None A156V Q30E/K Q30K, Y93H SMV + SOF, LDV/SOF R V36M, R155K V36M, R155K, A156T M28V, Q30R M28G, Q30R DCV + Peg-IFN/RBV Q30R, H58D ASV + DCV + BCV Q30G P29R, Q30G ASV + DCV 1b L28M, P32 del GLE/PIB 16 weeks 3PI-based (TVR, SIM, PTV), LDV/SOF+RBV Y56H, D168E V36M, Y56H, D168E K24Q, Y93H K24Q/R, Q30H, Y93H Q30R, L31M Q30R, L31M, H58D DCV + Peg-IFN/RBV, OBV/PTV/r + DSV Y56H, D168A Y56H, A156G, D168A M28T/V, Q30R, L31M NA OBV/PTV/r + DSV R155T, A156G, D168A Q30H, Y93H M28A, Q30H, H58D, Y93H MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print)

6 Adverse events and laboratory abnormalities, %
MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen Adverse events and laboratory abnormalities, % GLE/PIB 12 weeks N = 44 GLE/PIB 16 weeks N = 47 Any adverse event 75 68 Serious adverse event potentially related to treatment 2 4 Adverse event leading to discontinuation Adverse events in > 10% of patients Headache 14 23 Laboratory abnormalities ALT grade ≥ 3 Total bilirubin grade ≥ 3 Hemoglobin grade ≥ 3 MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print) 6

7 MAGELLAN-1 Study, Part 2: glecaprevir/pibrentasvir in genotype 1 or 4 with failure to DAA regimen
Summary In patients with prior PI failure and NS5A inhibitor-naïve, SVR12 of 100% after 12 or 16 weeks of glecaprevir/pibrentasvir In patients with prior failure to both PI and NS5A inhibitor, lower SVR12 were achieved In patients with with prior failure to NS5A inhibitor, SVR12 was 94% with 16 weeks of GLE/PIB, with no relapse Good tolerability, with no treatment-related serious adverse event No grade 3 or 4 laboratory abnormalities No discontinuation due to adverse events MAGELLAN-1, Part 2 Poordad F. Hepatology 2017 (Epub ahead of print) 7

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