1. ENDURANCE-4 Study: glecaprevir/pibrentasvir in genotype 4, 5 or 6
Design
Single arm
Open label
W12
≥ 18 years
HCV genotype 4, 5 or 6
BMI ≥ 18 kg/m2
Treatment-naïve or treatment-experienced with IFN or PEG-IFN + RBV or SOF + RBV + PEG-IFN
No cirrhosis **
Creatinine clearance ≥ 50 mL/min
No HBV or HIV co-infection
N = 121
GLE/PIB
SVR12
* Fibroscan® < 12.5 kPa or FibroTest® ≤ APRI < 1
GLE/PIB : 100/40 mg 3 tablets QD
Objective
SVR12 (HCV RNA < 15 IU/mL), by ITT
ENDURANCE-4
Asselah T. Clin Gastroenterol Hepatol 2017; Sept 22 (Epub ahead of print) 1

2. ENDURANCE-4 Study: glecaprevir/pibrentasvir in genotype 4, 5 or 6
Baseline characteristics and SVR12
GLE/PIB , N = 121
Mean age, years 53
Female, % 36
Race : White / Black, %
71 / 8
Mean BMI, kg/m2
25.7
Genotype 4 / 5 / 6, %
63 / 21 / 16
Median HCV RNA, log10 IU/mL
6.3
Fibrosis stage (%) : F0-F1 / F2 / F3
86 / 7 / 7
IL28B CC, % 25
Treatment-experienced, %
IFN-based
SOF-based 32
100
PPI use, % 9
SVR12, by ITT, n/N (%)
Genotype 4
Genotype 5
Genotype 6
120/121 (99% [95% CI : ])
75/76 (99%) * (1 discontinuation on D12)
26/26 (100%)
19/19 (100%)
ENDURANCE-4
Asselah T. Clin Gastroenterol Hepatol 2017; Sept 22 (Epub ahead of print) 2

3. ENDURANCE-4 Study: glecaprevir/pibrentasvir in genotype 4, 5 or 6
Adverse events and laboratory abnormalities
GLE/PIB, N = 121
Any adverse event, %
69%
Serious adverse event, n (%)
1 (0.8%) *
Adverse event leading to discontinuation, n (%)
3 (2.5%) **
Adverse events in > 10% of patients, %
Headache
Fatigue 21 17
Laboratory abnormalities
AST grade ≥ 2 (> 3 x ULN)
ALT grade ≥ 2 (> 3 x ULN)
Total bilirubin grade ≥ 3 ( > 3 x ULN)
* 1 patient with baseline risk factors discontinued treatment on D12 due to a transient ischemic attack (TIA); a second TIA occurred 24 days following discontinuation. This patient has not yet returned for SVR12 visit
** 3 patients presented with anxiety, heartburn, and transient ischemic attack, respectively. Two of the 3 patients achieved SVR12
ENDURANCE-4
Asselah T. AASLD 2016, Abs. 114 3

4. ENDURANCE-4 Study: glecaprevir/pibrentasvir in genotype 4, 5 or 6
Summary
99% of patients with genotype 4, 5 or 6 (120/121) without cirrhosis achieved SVR12 in ITT population following treatment with 12 weeks of GLE/PIB, with no virologic failures
100% SVR12 in mITT population
GLE/PIB was well tolerated
serious adverse events occurred in < 1% of patients
there were no grade 3 or higher laboratory abnormalities
discontinuation due to adverse events were rare
12-week treatment with the IFN- and RBV-free, once-daily GLE/PIB oral regimen can successfully treat patients with HCV genotype 4, 5, or 6, regardless of prior treatment experience or F0–F3 fibrosis status
ENDURANCE-4
Asselah T. Clin Gastroenterol Hepatol 2017; Sept 22 (Epub ahead of print) 4