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LDV/SOF Failure Study: LDV/SOF for retreatment
of genotype 1 with prior failure to LDV/SOF
 Design
Open-label
W24
Chronic HCV infection
Genotype 1
Failure to achieve SVR on
LDV/SOF-containing regimen
Compensated cirrhosis (liver biopsy or
Fibrotest > 0.75 + APRI > 2) allowed
No HBV or HIV co-infection
N = 41
LDV/SOF 90/400 x 1 qd
SVR12
 Objective
– Primary endpoint : SVR12 (HCV RNA < 15 IU/ml) by intention to treat, with
2-sided 95% CI, no statistical hypothesis
LDV/SOF Failure
Lawitz E. EASL 2015, Abs. O005
LDV/SOF Failure Study: LDV/SOF for retreatment
of genotype 1 with prior failure to LDV/SOF
Baseline characteristics
N = 41
Mean age, years
58
Female
17%
IL28B CC genotype
7%
HCV RNA log10 IU/ml, mean
6.2
Cirrhosis
46%
Genotype 1a
83%
Prior HCV treatment
LDV/SOF + RBV
LDV/SOF + GS-9669
80%
20%
Prior HCV treatment duration 8 weeks
Presence of NS5A RAVs
30 (73%)
19/30 (63%)
Prior HCV treatment duration 12 weeks
Presence of NS5A RAVs
11 (27%)
11/11 (100%)
LDV/SOF Failure
Lawitz E. EASL 2015, Abs. O005
LDV/SOF Failure Study: LDV/SOF for retreatment
of genotype 1 with prior failure to LDV/SOF
SVR12 (HCV RNA < 15 IU/ml)
100
%
100
71
75
68
74
100
80
100
80
69
60
50
46
50
33
25
0
N
41
22
19
30
11
11
30
11
16
14
All
No
Yes
8W
12W
No
Yes
None
1
≥2
Cirrhosis
Prior treatment
duration
Baseline
NS5A RAVs
Number of
NS5A RAVs
5
5
6
Q30R L31M Y93H/N
or
M28T
Type of single
NS5A RAVs
LDV/SOF Failure
Lawitz E. EASL 2015, Abs. O005
LDV/SOF Failure Study: LDV/SOF for retreatment
of genotype 1 with prior failure to LDV/SOF
 NS5B Resistance analysis
– Baseline : No NS5B resistance associated (S282T) or treatmentemergent (L159F, V321A) variants were detected
– At virologic failure : NS5B variants detected in 4 of 12 (33%) patients
• S282T (N = 2)
• L159F (N = 1)
• Double-mutant S282T + L159F (N = 1)
 Adverse events
–
–
–
–
–
Serious adverse events : 3
Discontinuation due to adverse event : 0
Grade 3 adverse events : 3 (none related to study drug)
Adverse events in ≥ 10% of patients : headache, fatigue
Grade 3 laboratory abnormality : 2
LDV/SOF Failure
Lawitz E. EASL 2015, Abs. O005
LDV/SOF Failure Study: LDV/SOF for retreatment
of genotype 1 with prior failure to LDV/SOF
 Summary
– 71% of patients who failed prior LDV/SOF-containing regimens
achieved SVR12 when retreated with LDV/SOF for 24 weeks
– The presence of baseline NS5A RAV(s), which was more likely to
develop with longer prior LDV/SOF treatment, was associated
with virologic failure
– Emergence of S282T was observed in 3 of 12 virologic failures
LDV/SOF Failure
Lawitz E. EASL 2015, Abs. O005