1. C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
Design
W12
18-70 years
HCV genotype 1-6
Treatment naïve or experienced (no prior DAA)
HCV RNA ≥ 10,000 IU/ml
No cirrhosis or compensated cirrhosis *
HIV co-infection allowed
No HBV co-infection
N = 250
RZR + UPR
SVR12 W0
2 cohorts: initial enrollment of 50 participants, and continue enrollment for a total of 250 patients if no safety criteria are met
* Liver biopsy or Fibroscan® > 12.5 kPa or FibroSure® > APRI > 2
RZR : 180 mg QD ; UPR : 450 mg QD
Objective
SVR12 (HCV RNA < 15 IU/mL), full analysis set (FAS) : all participants who received ≥ 1 dose of study medication ; mFAS : exclusion of participants with non-virologic failure
C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 61 1

2. C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
Baseline characteristics and SVR12
RZR + UPR 12W
N = 282
Mean age, years
49.5
Female, % 45
Race : White / Asian / Black, %
78 / 10 / 8
Cirrhosis, % 21
Genotype 1a / 1b / 2 / 3 / 4 / 5 / 6, %
17 / 11 / 17 / 22 / 21 / 6 / 8
IFN treatment-experienced, % 16
SVR12
FAS
mFAS **
90% * 92%
* 19 relapses , 2 discontinuations due to drug-related adverse events
** 8 patients excluded (7 discontinuations, 1 lost to follow-up)
C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 61 2

3. C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
SVR12, mFAS, by genotype, %
259 45 30 45 59 55 3 22
* GT1a: 3 relapses
** GT2 : 1 non-compliance, 1 discontinuation due to drug-related adverse event (insomnia and fatigue)
*** GT3: 14 relapses (SVR12 : 80% in non-cirrhotics vs 68% in cirrhotics)
**** GT6 : 1 relapse, 1 discontinuation due to drug-related adverse event (anxiéty and nausea)
C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 61 3

4. C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
SVR12, mFAS, according to baseline NS5A RAS in genotype 3 and 1a, %
No RAS
RAS present %
100 98
100 86 80 79 79 74 82 69 75 57 50 40 25 N 28 31 52 7 33 26 54 5 31 14 43 2
Any of 7
positions *
A30
S62
Y93
Any of 4
positions **
Y93
Genotype 3
Genotype 1a
* 24, 28, 30, 31, 58, 62, 93
** 28, 30, 31, 93 (detection par next-generation sequencing with 15% sensitivity
C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 61

5. C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
Adverse events, %
RZR + UPR 12W
N = 282
Any adverse event 61
Drug-related adverse event
Fatigue
Headache
33.3
7.8
7.4
Discontinuation due to adverse event
0.7
Serious adverse event
2.5
Discontinuation due to serious adverse event
C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 61 5

6. C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
Summary
Overall efficacy of the 2-drug regimen of ruzasvir + uprifosbuvir is suboptimal
Lower efficacy in genotype 3; baseline RAS account for many failures
High efficacy in other genotypes; potential impact of baseline Y93 RAS in GT1a, no impact of baseline RAS in other non-GT3 genotypes
Good safety profile
C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 69 6