1. Creatinine clearance ≥ 50 ml/min No HBV or HIV co-infection
ENDURANCE-2 Study: glecaprevir/pibrentasvir in genotype 2 without cirrhosis
Design
Randomisation
2 : 1
Double-blind
W12
W24
≥ 18 years,
HCV genotype 2
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 = 202
GLE/PIB
SVR12
Placebo
GLE/PIB
SVR12
N = 100
* Fibroscan® < 12.5 kPa or FibroTest® ≤ APRI < 1
GLE/PIB: 100/40 mg 3 tablets QD
Objective
SVR12 (HCV RNA < 15 IU/mL): non-inferiority, by ITT (exclusion of prior SOF failures), compared with historical rate of 95% (SOF + RBV), with lower margin of the 2-sided 95% CI > 89% ; superiority compared to the historical rate of 95%
ENDURANCE-2
Kowdley KV. AASLD 2016, Abs. 73 1

2. Baseline characteristics and SVR12
ENDURANCE-2 Study: glecaprevir/pibrentasvir in genotype 2 without cirrhosis
Baseline characteristics and SVR12
GLE/PIB , N = 202
Placebo, N = 100
Median age, years 58 59
Female, % 51 55
Race : Asian, % 34 32
Median BMI, kg/m2
24.7
26.1
Genotype 2a/c / 2b / 2i, %
38 / 23 / 0.5
40 / 21 / 0
Median HCV RNA, log10 IU/mL
6.25
6.39
Fibrosis stage (%) : F0-F1 / F2 / F3
76 / 9 / 15
85 / 9 / 6
IL28B CC, % 45 50
Treatment-experienced, %
IFN-based
SOF-based 30 90 10 29 93 7
PPI use, % 11
SVR12, n/N (%)
ITT *mITT (exclusion of 1 virologic failure who achieved SVR4)
195/196 (99%)
195/195 (100%)
* All 6 SOF-experienced patients achieved SVR12
ENDURANCE-2
Kowdley KV. AASLD 2016, Abs. 73 2

3. Adverse events and laboratory abnormalities, N (%)
ENDURANCE-2 Study: glecaprevir/pibrentasvir in genotype 2 without cirrhosis
Adverse events and laboratory abnormalities, N (%)
GLE/PIB , N = 202
Placebo, N = 100
Any adverse event
131 (65%)
58 (58%)
Serious adverse event
3 (1%) *
1 (1)**
Adverse event leading to discontinuation
Adverse events in > 10% of patients, %
Headache
Fatigue 12 11 10
Laboratory abnormalities
AST grade 2 (3-5 x ULN)
AST grade ≥ 3 (5 x ULN)
ALT grade 2 (3-5 x ULN)
ALT grade ≥ 3 (5 x ULN)
Total bilirubin grade 3 (3-10 x ULN)
2 (1%)
1 (0.5%)
2 (2%)
1 (1%)
6 (6%)
* One patient each experienced a broken ankle, hemorrhoids, and a bile duct stone; all were unrelated to treatment
** Rheumatoid arthritis, unrelated to treatment
ENDURANCE-2
Kowdley KV. AASLD 2016, Abs. 73 3

4. ENDURANCE-2 Study: glecaprevir/pibrentasvir in genotype 2 without cirrhosis
Summary
99% of patients with genotype 2 infection treated with GLE/PIB for 12 weeks achieved SVR12, with no virologic failures
The primary and secondary endpoints were achieved: SVR12 rate achieved with GLE/PIB treatment was superior to the 95% historical SVR12 rate of SOF + RBV
GLE/PIB was well tolerated:
There were no discontinuations due to adverse event
There were no serious adverse event related to GLE/PIB
GLE/PIB demonstrated a safety profile similar to that observed in patients receiving placebo
Achievement of SVR12 was not impacted by treatment experience or any other baseline factor
ENDURANCE-2
Kowdley KV. AASLD 2016, Abs. 73 4