1. No HBV or HIV co-infection
MAGELLAN-I Study, Part 1: Glecaprevir + Pibrentasvir in genotype 1 with failure to DAA regimen – Phase II
Design
W12
Randomisation
Open-label
N = 6 *
GLE 200 mg qd + PIB 80 mg qd
SVR12
18-70 years
HCV genotype 1
Failure to DAA regimen
HCV RNA > IU/ml
No cirrhosis
No HBV or HIV co-infection
GLE 300 mg qd + PIB 120 mg qd
+ RBV 800 mg qd
N = 22 **
SVR12
GLE 300 mg qd + PIB 120 mg qd
N = 22 **
SVR12
* Low dose arm halted (based on dose-findings results
across all genotypes)
** Randomisation stratified by genotype (1b or non-1b)
and prior treatment (NS5A inhibitor-experienced,
NS3/4A PI-experienced but NS5A inhibitor-naive, or other)
Objective
SVR12 (HCV RNA < 25 IU/ml), by ITT
MAGELLAN-I, Part 1
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2. Baseline characteristics
MAGELLAN-I Study, Part 1: Glecaprevir + Pibrentasvir in genotype 1 with failure to DAA regimen – Phase II
Baseline characteristics
GLE 200 mg + PIB 80 mg
N = 6
GLE 300 mg + PIB 120 mg
+ RBV 800 mg
N = 22
GLE 300 mg
+ PIB 120 mg
Median age, years 59 56
Female, % 50 9 18
Race : White , % 67 77 55
Median BMI, kg/m2 27 28
Genotype 1a, % 91 82
Median HCV RNA, log10 IU/ml
6.1
6.7
6.6
Fibrosis stage (%) : F0-F1 / F2 / F3
67 / 17 / 17
77 / 0 / 23
50 / 27 / 23
Study drug discontinuation, N 1
1 (breakthrough)
Prior regimen
PI-experienced, NS5A naïve, N = 25 ; NS5A-experienced, PI-naïve, N = 8
PI and NS5A-experienced, N = 17
SOF-experienced, N = 16
MAGELLAN-I, Part 1
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3. MAGELLAN-I Study, Part 1: Glecaprevir + Pibrentasvir in genotype 1 with failure to DAA regimen – Phase II
GLE PIB 120
GLE PIB RBV 800
GLE PIB 120
SVR12, ITT, % (95% CI)
SVR12, ITTm 6 22 95
(78-99) 86
(67-95) N= %
100
(61-100) 95 %
100 6 22 20
Breakthrough 1
Relapse
Lost to follow-up 2 1
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4. MAGELLAN-I Study, Part 1: Glecaprevir + Pibrentasvir in genotype 1 with failure to DAA regimen – Phase II
2 virologic failures in genotype 1a
Prior DAA regimen(s)
Response / Regimen
NS3 RAVs
NS5A RVAs
Baseline
Failure
OBV/PTV/r +
DSV + RBV
Breakthrough /
GLE + PIB
Y56H,
D168A/T
V36M,
D168A
M28V,
Q30R, H58C
M28G, Q30R,
H58C
DCV ; TVR + PR
Relapse / GLE + PIB + RBV
None
A156V
L31M
H58D
Q30R, L31M, H58D
SVR12 (ITTm) according to baseline RAVs
No RAVs
N = 10
NS3 RAVs only
N = 14
NS5A RAVs only
N = 11
NS3 & NS5A RAVs
N = 15
SVR12
100%
91%
93%
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5. Adverse events and laboratory abnormalities, %
MAGELLAN-I Study, Part 1: Glecaprevir + Pibrentasvir in genotype 1 with failure to DAA regimen – Phase II
Adverse events and laboratory abnormalities, %
GLE 200 mg + PIB 80 mg
N = 6
GLE 300 mg + PIB 120 mg
+ RBV 800 mg
N = 22
GLE 300 mg
+ PIB 120 mg
Any adverse event 83 86 77
Treatment-related serious adverse event
Adverse event leading to discontinuation
Adverse events in > 10% of patients
Headache
Fatigue
Nausea
Insomnia 17 23 36 27 18 14
Laboratory abnormalities, N
ALT grade ≥ 2 / AST grade ≥ 2
Total bilirubin grade 2
Alkaline phosphatase grade ≥ 2
Hemoglobin grade ≥ 2 3
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6. MAGELLAN-I Study, Part 1: Glecaprevir + Pibrentasvir in genotype 1 with failure to DAA regimen – Phase II
Summary
High SVR12 rates after 12 weeks of Glecaprevir + Pibrentasvir with only 2 virologic failures in 50 DAA-experienced genotype 1 patients without cirrhosis
Baseline NS3 and/or NS5A RAVs did not impact SVR12 (most patients (≥ 80%) had at least 1 baseline polymorphism in NS3 or NS5A)
RBV did not increase SVR12 rate
Good tolerability, with mild adverse events
No grade 3 or 4 laboratory abnormalities
No discontinuation due to adverse events
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