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Second generation PI
How to use and whom to treat?
Graham R Foster
Queen Marys University of London, London
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Case study: treatment naive
Hb, haemoglobin; WBC, white blood cell count; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate
aminotransferase; AFP, alfa-fetoprotein; HBsAg, hepatitis B antigen; HIVAb, human immunodeficiency virus antibody; HCV,
hepatitis C virus; USS, ultrasound scan.
Test Result Test Result
Hb 124 g/L HBsAg neg
WBC 4.0 x 109 /L HIVAb neg
Platelets 245 x 109 /L HCV RNA 880,000
copies/mL
ALP 97 IU/L Fibroscan 5.7 kPa
ALT 67 IU/L Genotype information:
AST 45 IU/L G1b
AFP 2.0 ng/μL IL28B genotype CC
Bilirubin 9 μmol/L Ultrasound:
Albumin 43 g/L Unremarkable
A 34-year-old female was found to be HCV-positive, previous IVDU
She wants to have a second child
Laboratory investigations
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IFN-based current and future options for
genotype 1 treatment-naïve patients
Cross comparison of studies cannot be carried out
SMV: simeprevir; FDV: faldaprevir; DCV: daclatasvir
SOF: sofosbuvir
74
66
80
73 72
65 64
90
20
60
100
40
80
SV
R (
%)
0
OPTIMIZE1 SPRINT-22 Pooled
QUEST1 & 23
COMMAND 15 STARTVerso1&24
274/
369
242/
366
419/
521
382/
521
378/
524
95/
147
94/
146
1. Buti M, Gastroenterology 2014;146:744–53
2. Boceprevir SmPC; 3. Jacobson I, et al. AASLD 2013. Poster 1122
4. Jensen DM, et al. AASLD 2013. Abstract 1088
5. Hézode, et al. AASLD 2012: Abstract 755;
6. Lawitz E, et al. N Engl J Med 2013;368:1878–
TVR/PR
(bid)
BOC/PR SMV/PR FDV
120mg/PR
FDV
240mg/PR
DCV
20mg/PR
DCV
60mg/PR SOF/PR
Neutrino6
295/
327
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What can we expect with simeprevir?
Patients deciding on treatment want to know what are their
chances of responding
What are the factors that influence outcome?
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Pooled QUEST 1&2 –
SVR in patients with mild disease
84 88 87
55 58 59
0
20
40
60
80
100
1.Jacobson I, et al. AASLD 2013. Poster 1122
2.Foster et al., EASL2014, Poster 1127
3. Adapted from Dore G, et al. APASL 2014. Poster
SV
R12 (
%)
317/378 106/192 191/217 64/110 179/202 61/103
SVR12 in METAVIR F0-F2 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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Pooled QUEST 1&2 –
SVR in patients with mild disease
84 88 87
55 58 59
0
20
40
60
80
100
1.Jacobson I, et al. AASLD 2013. Poster 1122
2.Foster et al., EASL2014, Poster 1127
3. Adapted from Dore G, et al. APASL 2014. Poster
SV
R12 (
%)
317/378 106/192 191/217 64/110 179/202 61/103
SVR12 in METAVIR F0-F2 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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Pooled QUEST 1&2 –
SVR in patients with mild disease
84 88 87
55 58 59
0
20
40
60
80
100
1.Jacobson I, et al. AASLD 2013. Poster 1122
2.Foster et al., EASL2014, Poster 1127
3. Adapted from Dore G, et al. APASL 2014. Poster
SV
R12 (
%)
317/378 106/192 191/217 64/110 179/202 61/103
SVR12 in METAVIR F0-F2 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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Pooled QUEST 1&2 –
SVR in patients with mild disease
84 88 87
55 58 59
0
20
40
60
80
100
1.Jacobson I, et al. AASLD 2013. Poster 1122
2.Foster et al., EASL2014, Poster 1127
3. Adapted from Dore G, et al. APASL 2014. Poster
SV
R12 (
%)
317/378 106/192 191/217 64/110 179/202 61/103
SVR rates were higher in the SMV/PR group compared
with PBO/PR irrespective of METAVIR score
SVR12 in METAVIR F0-F2 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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Pooled QUEST 1 & 2
SVR 12 in Genotype 1b meeting RGT
94 96 89 91
0
20
40
60
80
100
All genotype 1b patients METAVIR F0-F2
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4
and <25IU/mL undetectable at Week 12 Dore G, et al. APASL 2014. Poster
Po
rtio
n o
f p
ati
en
ts (%
)
252/267 224/252 193/202 176/193
Genotype 1b
96% of patients with F0-F2 were eligible to shorten treatment duration to 24 weeks.
91% achieved SVR12
Met RGT criteria SVR in RGT +
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Pooled QUEST 1 & 2: SVR 12 in Genotype 1b
94 96 89 91
0
20
40
60
80
100
All genotype 1b patients METAVIR F0-F2
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4
and <25IU/mL undetectable at Week 12 Dore G, et al. APASL 2014. Poster
Po
rtio
n o
f p
ati
en
ts (%
)
252/267 224/252 193/202 176/193
Genotype 1b
96% of patients with F0-F2 were eligible to shorten treatment duration to 24 weeks.
91% achieved SVR12
Met RGT criteria SVR in RGT +
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Pooled QUEST 1 & 2 –
SVR 12 in patients with severe disease (F4 meeting RGT)
91 86
92
83
0
20
40
60
80
100
All European patients METAVIR F4
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4
and <25IU/mL undetectable at Week 12 Foster et al., EASL2014, Poster 1127
Po
rtio
n o
f p
ati
en
ts (
%)
252/276 231/252 12/14 10/12
European patients
86% of patients with F4 were eligible to shorten treatment duration to 24 weeks.
83% achieved SVR12
Met RGT criteria SVR in RGT +
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Pooled QUEST 1 & 2 –
European patients (ITT) and IL-28
96
86
69
79
44
31
0
20
40
60
80
100
IL28B CC IL28B CT IL28B TT
Foster et al., EASL2014, Poster 1127
SV
R12 (
%)
72/75 33/42 143/166 37/84 24/35 5/16
higher SVR12 rates with SMV + PR compared with Pbo + PR, irrespective of IL28B
genotype
SVR12 by IL28B subgroup SMV + PR PBO + PR
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Pooled QUEST 1 & 2 –
SVR 12 by IL28B in patients meeting RGT
94 97
89
100
0
20
40
60
80
100
All genotype 1b IL28B CC
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4
and <25IU/mL undetectable at Week 12 Dore G, et al. APASL 2014. Poster
Po
rtio
n o
f p
ati
en
ts (
%)
252/267 224/252 65/67 65/65
Genotype 1b
97% of patients with IL28B CC were eligible to shorten treatment duration to 24
weeks. All of them achieved SVR12
Met RGT criteria SVR in RGT +
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Pooled QUEST 1 & 2 – SVR 12 by IL28B in
patients meeting RGT
91
83
92
76
0
20
40
60
80
100
All European patients IL28B TT
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4
and <25IU/mL undetectable at Week 12 Foster et al., EASL2014, Poster 1127
Po
rtio
n o
f p
ati
en
ts (
%)
252/276 231/252 29/35 22/29
European patients
83% of patients with IL28B TT were eligible to shorten treatment duration to 24
weeks. 76% achieved SVR12
Met RGT criteria SVR in RGT +
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Pooled QUEST 1 & 2 – SVR12 by demographic
and baseline disease characteristics
79 82
67
82
74
85
78
92
48 53
36
51
41
52
40
77
0
20
40
60
80
100
Male Female Black Caucasian BMI ≥30 kg/m2
BMI <25kg/m2
HCV RNA>800,000
IU/mL
HCV RNA ≤800,000
IU/mL
SV
R12 (
%)
SMV + PR PBO + PR
Jacobson I, et al. AASLD 2013. Poster 1122
227/
288
72/
151 192/
233
60/
113
29/
43
5/
14
378/
464
124/
245
84/
113 29/
70
175/
207
53/
103
323/
417
78/
194
96/
104
54/
70
2 2
Significantly higher SVR rates were observed with SMV + PR compared to PR
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What can we expect with simeprevir?
Patients deciding on treatment want to know what are their
chances of responding
For this young European female the chance of an SVR is
>90% with simeprevir
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Treatment regimen for naive and prior relapser
SMV + PR PR
0 12 24 Week
Russian SmPC Simeprevir *HCV genotype 1a patients, if testing is available, patients should be tested for the
presence of virus with the NS3 Q80K polymorphism before starting treatment
Stopping rules: discontinue SMV + PR if HCV RNA ≥ 25 IU/mL at treatment
Week 4, discontinue PR if ≥ 25 IU/mL at treatment Week 12 or week 24
Fixed treatment duration for treatment naïve and prior relpaser in GT 1*:
• Total treatment duration is 24 weeks irrespective of fibrosis stage
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Safety in treatment naive European patients
*Without regard to peginterferon and ribavirin
n (%)
First 12 weeks Entire treatment phase
SMV + PR
(n=276)
Pbo + PR
(n=142)
SMV + PR
(n=276)
Pbo + PR
(n=142)
At least 1 AE, n (%) 260 (94.2) 135 (95.1) 266 (96.4) 137 (96.5)
Grade 1 or 2, n (%) 191 (69.2) 98 (69.0) 179 (64.9) 90 (63.4)
Grade 4, n (%) 9 (3.3) 2 (1.4) 12 (4.3) 3 (2.1)
At least 1 SAE, n (%) 8 (2.9) 2 (1.4) 12 (4.3) 3 (2.1)
AEs leading to discontinuation
of SMV/ PBO*
6 (2.2) 1 (0.7) 6 (2.2) 1 (0.7)
AEs of special interest
Increased bilirubin 34 (12.3) 6 (4.2) 35 (12.7) 6 (4.2)
Rash (any type) 63 (22.8) 13 (9.2) 73 (26.4) 23 (16.2)
Pruritus 56 (20.3) 21 (14.8) 74 (26.8) 38 (26.8)
Photosensitivity conditions 9 (3.3) 0 (0.7) 9 (3.3) 1 (0.7)
Grade 3 or 4 laboratory parameters, n (%)
Haemoglobin 1 (0.4) 4 (2.8) 2 (0.7) 4 (2.8)
Bilirubin 9 (3.3) 1 (0.7) 9 (3.3) 1 (0.7)
Neutrophils 44 (16.0) 24 (16.9) 65 (23.6) 38 (26.8)
Foster et al., EASL2014, Poster 1127
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Can we shorten treatment duration further?
Is 12 weeks enough?
Response-guided therapy of 12 or 24 weeks guided by HCV RNA measurements at treatment weeks
2, 4 and 8
– All patients: 12 weeks of triple therapy*; stop all therapy after Week 12 if HCV RNA <25 IU/mL
(detectable or undetectable) at Week 2 AND <25 IU/mL undetectable at Week 4 AND <25 IU/mL
undetectable at Week 8; otherwise continue treatment
*Unless a virologic stopping rule is met
PR: Peg-IFNα-2a 180 µg/wk + RBV 1000–1200 mg/day www.clinicaltrials.gov (NCT01846832)
Week 12 Week 24 Week 36 Week 48
SMV 150 mg qd + PR
Post-treatment follow up
Continue PR to
Week 24
Week 4
Post-treatment follow up
Treatment-naïve patients:
• GT 1 & 4
• F0–F2
• irrespective of Q80K, irrespective of IL28B
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Case study: prior relapser
A 53-year-old male with chronic HCV
January 2009: patient was treated with PR but relapsed
Concomitant diseases: depression (well controlled by antidepressants);
BMI 28 kg/m2
HCV-RNA: 266,575 IU/mL; genotype 1b; IL28B-GT: CT
Fibrosis score: F4;
Albumin and prothrombin time normal; no clinical signs of
decompensated liver disease
i.v., intravenous; BMI, body mass index; US, ultrasound
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What can we expect with simeprevir?
Patients deciding on their second course of treatment want it
to be their last!
Who is going to be cured second time around?
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First generation PIs in treatment experienced
patients
84
69
47
0
20
40
60
80
100
122/145 100/146
75
52
41
0
20
40
60
80
100
20/49 110/238 30/58 77/103
Telaprevir Boceprevir
Relapser Partial
responder
null
responder
Relapser Partial
responder
null
responder
REALIZE1 ATTAIN2 RESPOND 23 PROVIDE4
SV
R (
%)
SV
R (
%)
1.INCIVO (telaprevir) EU SmPC 2.Reddy KR, et al. APASL 2014. Oral presentation
3.VICTRELIS (boceprevir) EU SmPC 4. Vierling J, et al. DDW 2013. Abstract 869c
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Current and future IFN based options for
genotype 1 in treatment-experienced patients
79
70
44
70
58
33 33
0
20
40
60
80
100
SV
R (
%)
Cross comparison of studies cannot be carried out. ¶in Japanese patients only
1. Forns X, et al. Gastroenterology 2014;146:1669–1679
2. Reddy K, et al. APASL 2014; 3. Jacobson I, et al. AASLD 2013. Abstract 1100
4. Lawitz E, et al. EASL 2014. Abstract O165; 5. Suzuki F, et al. APASL 2012
Some data on
re-treatment
with SOF/PR,
but no Phase
II or III data
available 101/
145
102/
234
206/
260
69/
99
33/
57
48/
145 3/9
Relapsers
Partial
responders Nulls
Non
responders Relapsers
Partial
responders Nulls Nulls
SMV
150 mg*/PR
PROMISE1
SMV
150 mg*/PR
ATTAIN2
FDV* 240mg/PR (12 week arm)
STARTVerso-33
DCV
60 mg*/PR¶
COMMAND-25
SOF/PR
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PROMISE – SVR by fibrosis stage in prior relapser
74
85 84
26 30
25
0
20
40
60
80
100
1. Forns X, et al. Gastroenterology 2014;146:1669–1679
2.Forns et al., EASL2014
3.Gane et al., APASL2014
SV
R12 (
%)
29/39 5/19 23/27 3/10 16/19 2/8
SVR12 in METAVIR F4 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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PROMISE – SVR by fibrosis stage in prior relapser
74
85 84
26 30
25
0
20
40
60
80
100
1. Forns X, et al. Gastroenterology 2014;146:1669–1679
2.Forns et al., EASL2014
3.Gane et al., APASL2014
SV
R12 (
%)
29/39 5/19 23/27 3/10 16/19 2/8
SVR12 in METAVIR F4 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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PROMISE – SVR by fibrosis stage in prior relapser
74
85 84
26 30
25
0
20
40
60
80
100
1. Forns X, et al. Gastroenterology 2014;146:1669–1679
2.Forns et al., EASL2014
3.Gane et al., APASL2014
SV
R12 (
%)
29/39 5/19 23/27 3/10 16/19 2/8
SVR12 in METAVIR F4 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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PROMISE – SVR by fibrosis stage in prior relapser
74
85 84
26 30
25
0
20
40
60
80
100
1. Forns X, et al. Gastroenterology 2014;146:1669–1679
2.Forns et al., EASL2014
3.Gane et al., APASL2014
SV
R12 (
%)
29/39 5/19 23/27 3/10 16/19 2/8
SVR rates were higher in the SMV/PR group compared
with PBO/PR irrespective of METAVIR score
SVR12 in METAVIR F4 patients
Overall1 European patients2 Genotype subtype 1b3
SMV + PR PBO + PR
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PROMISE – SVR 12 by fibrosis stage in
Genotype 1b patients meeting RGT
95 95 89 89
0
20
40
60
80
100
All genotype 1b patients METAVIR F4
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4
and <25IU/mL undetectable at Week 12 Gane E, et al. APASL 2014. Poster
Po
rtio
n o
f p
ati
en
ts (%
)
141/149 125/141 18/19 16/18
Genotype 1b
95% of patients with F4 were eligible to shorten treatment duration to 24 weeks.
89% achieved SVR12
Met RGT criteria SVR in RGT +
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Patients with on treatment response at week 4*
achieve high SVR
For prior treatment failures - if you have not got an
early response at week 4 you won’t do well with
simeprevir
BUT
If you do have an early response you have a very
high chance of response with simeprevir
*Early response at week 4: HCV RNA <25IU/ml Forns X, et al. AASLD 2014
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89
78
64
53
34
19
0
20
40
60
80
100
CC CT TT
SMV + PR: PROMISE – SVR12 by IL28B genotype
P<0.001, based on a logistic regression model with factors for treatment
group, baseline HCV RNA, HCV 1 subtype and IL28B genotype Forns X, et al. Gastroenterology 2014;146:1669–1679
SV
R12 (
%)
137/167 40/98 32/44 3/15 29/39 5/19
Significantly higher SVR12 rates with SMV + PR compared with Pbo +
PR, irrespective of IL28B genotype
SMV + PR PBO + PR
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76 75
90
6 2 0
0
20
40
60
80
100
CC CT TT
PROMISE – RVR by IL28B genotype in prior
relapsers
P<0.001, based on a logistic regression model with factors for treatment
group, baseline HCV RNA, HCV 1 subtype and IL28B genotype Forns X, et al. AASLD 2014
RV
R (
%)
47/62 2/33 125/167 2/81
28/31 0/16
RVR rates were significantly higher with SMV + PR vs Pbo + PR,
regardless of IL28B genotype
SMV + PR PBO + PR
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SMV + PR: PROMISE – SVR12 by IL28B in
genotype 1b prior relapsers who met RGT
P<0.001, based on a logistic regression model with factors for treatment group, baseline HCV RNA,
HCV 1 subtype and IL28B genotype
RGT criteria: HCV RNA <25 IU/mL, detectable/undetectable at Week 4 and <25IU/mL undetectable at Week 12 Gane et al. APASL 2014
SV
R12 (
%)
All genotype1b patients achieved high SVR rates irrespective of their
IL28B genotype
95 97 94 95 89
97 90
68
0
20
40
60
80
100
All genotype1b
CC CT TT
141/
149
125/
141
32/
33
31/
32
90/
96
81/
90
19/
20
13/
19
Patients who met
RGT
SVR12 of patients
who met RGT
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Safety in treatment experienced European patients
*Also included photosensitivity events Forns et al., EASL2014
First 12 weeks Entire treatment phase
SMV/PR
(N=184)
PBO/PR
(N=90)
SMV/PR
(N=184)
PBO/PR
(N=90)
Grade 3 / 4 AEs, % 17.9 / 1.6 17.8 / 2.2 22.8 / 3.3 26.7 / 4.4
Any SAE, % 1.7 1.2 5.6 9.2
Most frequently occurring AEs, %
Fatigue 31.5 35.6 32.1 36.7
Headache 30.4 31.1 31.5 31.1
Pruritus 26.6 20.0 32.1 33.3
Pyrexia 26.1 25.6 29.3 27.8
Influenza-like illness 29.9 20.0 29.9 20.0
AEs of clinical interest, %
Rash (any type)* 16.3 6.7 20.7 15.6
Photosensitivity conditions (any type) 4.3 0 4.3 0
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Treatment regimen in Russia for naive and prior
relapser1
Treatment-naive and prior relapser,
F0-F4 SMV + PR PR
0 12 24 Week
Russian SmPC Simeprevir
1.Including HCV/HIV co-infected patients
*HCV genotype 1a patients, if testing is available, patients should be tested for the presence of virus with the
NS3 Q80K polymorphism before starting treatment
Stopping rules: discontinue SMV + PR if HCV RNA ≥ 25 IU/mL at treatment
Week 4, discontinue PR if ≥ 25 IU/mL at treatment Week 12 or week 24
Fixed treatment duration for treatment naïve and prior relpaser with SMV +
PR in genotype 1* irrespective of fibrosis stage
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Treatment regimen for partial and null responder1
1includes HIV/HCV coinfected patients.
*HCV genotype 1a patients, if testing is available, patients should be tested for the presence of virus with the
NS3 Q80K polymorphism before starting treatment
0 12 24 48 Weeks
Prior partial and null responders
F0−F4
4
If HCV RNA ≥25 IU/mL,
discontinue SMV + PR If HCV RNA ≥25 IU/mL,
discontinue PR
SMV + PR PR
Stopping rules
Recommended combination and treatment duration with SMV + PR
in genotype 1*
Russian SmPC Simeprevir
Partial and Null responder will be treated for a total duration of 48 weeks
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Simeprevir in Treatment Experienced Patients
A good choice with good predictability criteria
What about the alternatives?
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IFN free regimens for genotype 1 treatment-
experienced patients
10
96 98
82
94-96 99
87 95
0
20
40
60
80
100
120
Cross comparison of studies cannot be carried out
*METAVIR score derived from fibrotest (classified according to manufacturers website)
Patients with F4 were required to have no evidence of cirrhosis based upon a biopsy
¶ GT1b patients only
1.Gane et al., N Engl J Med 2013;368:34-44
2.Lawitz et al., EASL2014. LB O165
3. Sulkowski MS, et al. N Engl J Med 2014;370:211–21
4. Manns M et al. EASL 2014. Abstract O166
5.Afdhal N, et al. N Engl J Med. 2014; 370:1483–1493
6.Poordad F, et al. N Engl J Med 2014 [Epub ahead of print]
SV
R (
%)
SOF/SMV
±RBV
12 wks
SOF/DCV±RBV
24 wks
1/10
ELECTRON1
40/41
SOF + LDV
±RBV
12 wks
3D + RBV
12 wks
3D + RBV
24 wks
Null responder Treatment
experienced
TURQUOISE-II6
SOF
+ RBV
12 wks
100% cirrhotics No cirrhotics
21/22
COSMOS2 A14440403
PI
experienced
168
/205
Partial/ Null
responder¶
Hallmark
Dual4
59/
62
65/
75
DCV +ASV
24 wks
Null responder
No cirrhotics*
SOF + LDV
±RBV
24 wks
209
/220
218
/220
ION-25
100% cirrhotics 31% cirrhotics 15-17% cirrhotics
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COSMOS: SVR12 in naïve and prior null responder with F3/F4
Cohort 2; intent-to-treat population
Lawitz E, et al. EASL 2014. Oral presentation O165
EU SmPC Simeprevir
SMV + SOF + RBV SMV + SOF
SMV + SOF + RBV SMV + SOF
SMV + SOF ± RBV
24 weeks
100
SV
R1
2 (
%)
12 weeks
80
60
40
20
0
100
80
60
40
20
0
93 100
93 93 100
80
60
40
20
0 82/87
Overall
28/30 16/16 25/27 13/14
94
SMV + SOF ± RBV for 12 weeks is approved by EMA
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Improved HCV treatments continue to be developed
but when can we expect these treatments?
Jul–Dec Jan–Jun Jul–Dec Jan–Jun Jul–Dec Jan–Jun Jul–Dec Jan–Jun Jul–Dec
Telaprevir
Boceprevir
Interferon Free
Triple therapy
Faldaprevir*
(G1)
Sofosbuvir
(G1,4,5,6)
Sofosbuvir
+
RBV
G2/3 +
Asunaprevir*
Daclatasvir*
±
BMS-325*
Daclatasvir*
(G1, 2, 3, 4)
Sofosbuvir+
Ledipasvir
FDC*
Ombitasvir*
Dasabuvir*
+
ABT-450*/r
RBV
+
±
2011 2012 2013 2014 2015
IFN
-fre
e
IFN
-ba
se
d
Simeprevir
(G1, 4)
EMA approvals
RBV
±
Protease inhibitor
Nuc inhibitors
NS5A
NS5B inhibitor
Nuc: nucleotide polymerase inhibitor; NS5A: hepatitis C virus non-structural protein 5a protease inhibitor
*Not yet approved in Europe
Sofosbuvir
Simeprevir
+
RBV
±
G1/4
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Development of SMV in IFN-free based regimens in
HCV genotype 1 patients
Clinicaltrials.gov
Ongoing/future IFN-free studies with SMV
Genotype 1b, Post-OLT, treatment-naïve
and null responder
SATURN: SMV + DCV + RBV
(NCT01938625)
Treatment-naïve, HCV GT 1b/4/6 and
treatment-naïve/exp HCV GT1a/b
HELIX 1&2: SMV +
samatasvir ± TMC647055/r ±
RBV (NCT01852604)
Treatment-naïve and treatment
experienced, 8 vs 12 weeks, non F4
OPTIMIST 1
SMV + SOF (NCT02114177)
Treatment-naïve and experienced
12 weeks, including F4
OPTIMIST 2
SMV + SOF (NCT02114151)
Phase II
Pha
se I
II
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Conclusion
Second generation PIs demonstrate high SVR rates with an
improved safety profile
– The European subpopulation and GT 1b patients achieve even
higher SVR rates
– SMV was generally well tolerated in the European HCV
genotype 1 patient population and most AEs were Grade 1 or 2
Treatment naïve and prior relapser will be treated with a
simplified fixed treatment duration of 24 weeks with a once
daily regimen of SMV+PR irrespective of their fibrosis stage