1. EXPEDITION-IV Study: glecaprevir/pibrentasvir in patients with renal impairment
Design
Single arm
Open label
W12
≥ 18 years,
HCV genotype 1 to 6
HCV RNA ≥ 1000 IU/mL
eGFR (MDRD) < 30 mL/min
Treatment-naïve or treatment-experienced with IFN/PEG-IFN ± RBV or SOF + RBV ± PEG-IFN
Compensated cirrhosis allowed
No HBV or HIV co-infection
Acute renal failure excluded
N = 104
GLE/PIB
SVR12
GLE/PIB : 100/40 mg 3 tablets QD
Objective
SVR12 (HCV RNA < 15 IU/mL)
EXPEDITION-IV
Gane E. AASLD 2016, Abs. LB-11 1

2. EXPEDITION-IV Study: glecaprevir/pibrentasvir in patients with renal impairment
Baseline characteristics and SVR12
GLE/PIB , N = 104
Median age, years 57
Female, % 24
Race : Black, % 25
Median BMI, kg/m2 26
Genotype 1a / 1b / 1 other / 2 / 3 / 4 / 5 / 6, %
22 / 28 / 2 / 16 / 11 / 19 / 1 / 1
Median HCV RNA, log10 IU/mL
5.9
Compensated cirrhosis, % 19
IL28B CC, % 23
Treatment-experienced, %
IFN-based
SOF-based 42 95 5
PPI use, % 41
Chronic kidney disease stage, %
eGFR ml/min/1.73 m2
eGFR < 15 ml/min/1.73 m2 (hemodialysis) 12
88 (82)
SVR12, by ITT, n/N (%)
102/104 (98%) [1 discontinuation, 1 LTFU]
EXPEDITION-IV
Gane E. AASLD 2016, Abs. LB-11 2

3. Adverse events and laboratory abnormalities, %
EXPEDITION-IV Study: glecaprevir/pibrentasvir in patients with renal impairment
Adverse events and laboratory abnormalities, %
GLE/PIB , N = 104
Any adverse event 71
Serious adverse event
related to study drug 24
Adverse event leading to discontinuation
4 *
Death
1 **
Adverse events in > 10% of patients, %
Pruritus
Fatigue
Nausea 20 14 12
Laboratory abnormalities, %
Hemoglobin grade ≥ 3 (6.5-8 g/dL)
AST grade ≥ 2 (> 3 x ULN)
ALT grade≥ 2 (> 3 x ULN)
Total bilirubin grade ≥ 3 ( > 3 x ULN)
* 1) diarrhea, 2) pruritus, 3) pulmonary edema, hypertensive cardiomyopathy with congestive failure, and 4) hypertensive crisis
** Serious adverse event of cerebral hemorrhage, not related to study drug, at post-treatment W2
EXPEDITION-IV
Gane E. AASLD 2016, Abs. LB-11 3

4. EXPEDITION-IV Study: glecaprevir/pibrentasvir in patients with renal impairment
Summary
GLE/PIB (300 mg/120 mg QD) achieved high efficacy in patients with stage 4 or 5 chronic kidney disease and HCV infection
98% ITT SVR12 rate across all major HCV genotypes
No virologic failures
GLE/PIB was well tolerated with a favorable safety profile in this difficult-to-treat population:
No drug-related serious adverse event
No grade ≥ 2 laboratory abnormalities in ALT or AST
EXPEDITION-IV
Gane E. AASLD 2016, Abs. LB-11 4