Asselah T. AASLD 2015, Abs. 714

Randomisation1:1

Open-label

18-65 yearsHCV genotype 4

HCV RNA ≥ 1,000 IU/mlNaïve or pre-treated with

PEG-IFN + RBV (Part I)Naïve or pre-treated with

PEG-IFN + RBV or SOF + RBV + PEG-IFN (Part II)Compensated cirrhosis

No HBV or HIV co-infection

N = 59

W12 W24

OPV/PTV/r + RBV

OPV/PTV/r + RBV

Naïve or pretreated PEG-IFN + RBV

W16

N = 61

N = 60

N = 10Part II, exploratoryNo randomisation

Part-I

Design

Objective– SVR12 (HCVRNA < LLOQ), with 2 sided 97.5% confidence interval, treatment-emergent

adverse events ; HCV N5B amplified and sequenced in all baseline samples

Treatment regimens– Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg qd = 2 tablets– Weight-based RBV (bid dosing)

OPV/PTV/ + RBV (Naïve or pre-treated with PEG-IFN + RBV)

OPV/PTV/r (Pre-treated with SOF + RBV ± PEG-IFN)

AGATE-I

AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis

OBV/PTV/r + RBV 12W N = 60

OBV/PTV/r + RBV 16W N = 60

Mean age, years 58 57Female 23.3% 36.7%Mean BMI, kg/m2 28.1 28.3Mean HCV RNA, log10 IU/Ml 6.2 6.0GT4 subtype by phylogenetic analysis (%)

4a / 4c / 4d / 4e /4f / 4h / 4k / 4l / 4n / 4o / 4p / 4 q / 4r / 4t

57.6 / 3.4 / 20.3 / 1.7 / 1.7 / 0 / 3.4 / 0 / 3.4 /

0 / 3.4 / 1.7 / 1.7 / 1.7

49.2 / 3.3 / 31.1 / 0 / 3.3. / 1.6 / 3.3. / 3.3 / 0 /

1.6 / 0 / 0 / 0 / 0Treatment-naïve 31 (51.7%) 29 (48.3%)Treatment-experienced

Null responsePartial responseRelapse

29 (48.3%)1757

31 (51.7%)1678

Mean platelet count (x 109/l) 159 143Mean albumin (g/l) 42 ± 3.7 42 ± 4.3History of diabetes 35% 21.7%

Baseline characteristics (AGATE-I, Part I)

Asselah T. AASLD 2015, Abs. 714AGATE-I

AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis

Asselah T. AASLD 2015, Abs. 714

AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis

AGATE-I

SRV12 rates by treatment arms

Arm A12 weeks

96

0

20

40

60

80

100

Arm B16 weeks

100

52/54* 49/49*

%

* All patients have not yet reached pst-treetment W12; SVR4 : 97% and 100%, respectively

OBV/PTV/r + RBV 12WN = 54

OBV/PTV/r + RBV 16WN = 49

Non-response 2 (3.7%) 0

On-treatment virologic failure 1 (1.9%) * 0

Premature study drug discontinuation 1 (1.9%) (at Day 1) 0

Missing SVR12 data 0/54 0

Relapse by 12 weeks post-treatment 0/52 0

Reasons for not achieving SVR12

* GT4a, Fibroscan : 15.6 kPaNS3 : no baseline polymorphism ; no treatment-emergent NS3 RAVSNS5B : at baseline : P58L ; at VF : emergence of L28L/M and Y93Y/H + P58L

Asselah T. AASLD 2015; Abs. 714AGATE-I

AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis

OBV/PTV/r + RBV 12W N = 60

OBV/PTV/r + RBV 16W N = 60

Any treatment-emergent adverse event 47 (78.3%) 55 (91.7%)

Adverse event leading to discontinuation 0 0

Serious adverse event 4 (6.7%) 4 (6.7%)

Severe adverse event 2 (3.3%) 2 (3.3%)

Death 0 0

Adverse events occurring in ≥ 10% in either group, %AstheniaFatigueHeadacheAnemiaPruritusNauseaDizzinessHemoglogin decreasedInsomnia

18.316.723.315.08.3

10.05.05.08.3

31.731.723.318.323.313.315.013.310.0

ALT ≥ Grade 2 (> 3 x ULN) / AST ≥ Grade 2 (> 3 x ULN) 3 (5.1%) / 1 (1.7%) 0 / 0

Total bilirubin grade 3 (> 3-10 x ULN) 5 (8.5%) 3 (5.0%)

Treatment-emergence adverse events (AGATE-I, Part I)

Asselah T. AASLD 2015; Abs. 714AGATE-I

AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis

Summary

– High SVR rates were achieved in patients with HCV genotype 4 infection and compensated cirrhosis with OBV/PTV/r + RBV administered for 12 weeks or 16 weeks : SVR12 was 96% and 100%, respectively

– OBV/PTV/r + RBV was well tolerated with no discontinuations due to adverse events

– All serious adverse events were deemed not related to study drugs

Asselah T. AASLD 2015; Abs. 714AGATE-I

AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis