ENDURANCE-3 Study: glecaprevir/pibrentasvir
versus sofosbuvir + daclatasvir in genotype 3
 Design
Randomisation
2:1
Double-blind
≥ 18 years, HCV genotype 3
Treatment-naïve
HCV RNA > 1 000 IU/mL
No cirrhosis (Metavir ≤ F3)
No HBV or HIV co-infection
ALT/AST < 10 x ULN, albumin > LLN
N = 233
N = 115
W12
GLE/PIB
SVR12
SOF + DCV
SVR12
W8
Third arm, non randomised, added after
the completion of the phase 2 study
N = 157
GLE/PIB
SVR12
‒ Glecaprevir/pibrentasvir: 100/40 mg 3 tablets QD
‒ Sofosbuvir: 400 mg 1 tablet QD + daclatasvir 60 mg 1 tablet QD
 Objective
– Non-inferiority of SVR12 of GLE/PIB compared to SOF + DCV
(lower bound of 95% CI of the difference: - 6%)
ENDURANCE-3
Foster G. EASL 201, Abs. GS-007
ENDURANCE-3 Study: glecaprevir/pibrentasvir
versus sofosbuvir + daclatasvir in genotype 3
Baseline characteristics
GLE/PIB 12W
N = 233
SOF + DCV 12W
N = 115
GLE/PIB 8W
N = 157
Median age, years
48
49
47
Female, %
48
55
41
Race: White, %
88
90
85
BMI, median kg/m2
25
25
26
History of injection drug use, %
64
63
66
Median HCV RNA, log10 IU/mL
6.1
6.0
6.1
86 / 5 / 9
84 / 7 / 9
78 / 5 /17
99
100
99
Fibrosis stage: F0-F1 / F2 / F3, %
Subtype genotype 3a, %
ENDURANCE-3
Foster G. EASL 201, Abs. GS-007
ENDURANCE-3 Study: glecaprevir/pibrentasvir
versus sofosbuvir + daclatasvir in genotype 3
SVR12 by intention-to-treat analysis, %
100
95
97
95
233
115
157
GLE/PIB 12W
SOF + DCV 12W
GLE/PIB 8W
80
60
40
20
0
Breakthrough/relapse (N)
Failure due to other reasons
Lost o follow-up/Missing SVR12
1/3
3
4
0/ 1
1
2
1/5
0
2
 Both GLE/PIB treatments met non-inferiority criteria (lower bound of the 95%
confidence interval above - 6%)
 GLE/PIB 12W vs SOF + DCV : -1.2% (95% CI: -5.6 to 3.1)
 GLE/PIB 8W vs GLE/PIB 12W : -0.4% (95% CI : -5.4 to 4.6)
ENDURANCE-3
Foster G. EASL 201, Abs. GS-007
ENDURANCE-3 Study: glecaprevir/pibrentasvir
versus sofosbuvir + daclatasvir in genotype 3
SVR12 by baseline polymorphisms *
GLE/PIB 12W
N = 233
SOF + DCV 12W
N = 115
GLE/PIB 8W
N = 157
NS3 RASs only
26/26 (100%)
-
14/15 (93%)
NS5A RASs only
35/36 (97%)
20/21 (95%)
35/36 (94%)
6/7 (86%)
-
5/7 (71%)
151/153 (99%)
89/89 (100%)
94/95 (99%)
NS3 + NS5A RASs
None
* Detected by next-generation sequencing using 15% detection threshold
 3% of patients (N = 10) had virologic failure
- Common baseline RASs
• NS3A: A166S, N = 3
• NS5A: A30K, N = 5
- RASs at failure
A30K + Y93H in 5/10
ENDURANCE-3
Foster G. EASL 201, Abs. GS-007
ENDURANCE-3 Study: glecaprevir/pibrentasvir
versus sofosbuvir + daclatasvir in genotype 3
Adverse events and laboratory abnormalities, N (%)
GLE/PIB 12W
N = 233
SOF + DCV 12W
N = 115
GLE/PIB 8W
N = 157
177 (76%)
80 (70%)
98 (62%)
Serious adverse event *
5 (2%)
2 (2%)
3 (2%)
Adverse event leading to discontinuation
3 (1%)
1 (1%)
0
26
19
14
20
14
13
20
13
12
0
0
1 (< 1)
1 (1)
0
0
0
1 (1)
0
Any adverse event
Adverse events in > 10% of patients, %
Headache
Fatigue
Nausea
Laboratory abnormalities, N (%)
ALT grade ≥ 3 (5 x ULN)
Total bilirubin > 3 x ULN
Neutrophil count < 1.0 x 109/L
* No serious adverse event was assessed as related to study drugs
ENDURANCE-3
Foster G. EASL 201, Abs. GS-007
ENDURANCE-3 Study: glecaprevir/pibrentasvir
versus sofosbuvir + daclatasvir in genotype 3
 Summary
– Glecaprevir/pibrentasvir achieved high efficacy in non-cirrhotic,
treatment-naïve patients with genotype 3
– 12 weeks of GLE/PIB was not inferior to 12 weeks of SOF+DCV
– 8 weeks of GLE/PIB was not inferior to 12 weeks of GLE/PIB
– Treatment was well-tolerated
– Of note, resistance analysis observed that the combination of NS3 +
NS5A RAs reduced SVR12 to 86% (GLE/PIB 12 weeks) and 71%
(GLE/PIB 8 weeks)
ENDURANCE-3
Foster G. EASL 201, Abs. GS-007