Second generation PI
How to use and whom to treat?
Graham R Foster
Queen Marys University of London, London
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
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
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?
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
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
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
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
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 +
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 +
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 +
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
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 +
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 +
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
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
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
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
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
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
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?
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
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
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
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
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
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
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 +
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
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
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
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
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
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
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
Simeprevir in Treatment Experienced Patients
A good choice with good predictability criteria
What about the alternatives?
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
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
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
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
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
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