Hepatitis treatment viena

TREATMENT HEPATITIS C
VALENTIN SOSA DZUL
RESIDENTE DE MEDICINA INTERNA 2°
UNIDAD MEDICA DE ALTA ESPECIALIDAD “ADOLFO
RUIZ CORTINES”
VERACRUZ, VERCZ JUNIO 2015

clinicaloptions.com/hepatitis
HCV Approved Therapies
April 22-26, 2015
Vienna, Austria
Highlights From EASL:
CCO Independent Conference Coverage
of the 2015 Annual Meeting of the European Association for the Study of
the Liver*
*CCO is an independent medical education company that
provides state-of-the-art medical information to healthcare
professionals through conference coverage and other
educational programs.
This program is supported by educational grants from
AbbVie, Gilead Sciences, and Merck.

EASL 2015 HCV*: Tx-Naive or PR-Exp’d,
GT1, 4, 5, or 6, Without Cirrhosis
Regimen
HCV Genotype
1a 1b 4 5 or 6
SOF + PR 12 wks 12 wks 12 wks
SMV + PR 12 wks (naive or relapse)
24 wks (partial/null)
12 wks (naive or relapse)
Not
recommended
LDV/SOF 8-12 wks,†
no RBV 12 wks, no RBV 12 wks, no RBV
OBV/PTV/RTV
+ DSV
12 wks
+ RBV
12 wks,
no RBV
Not recommended Not
recommended
OBV/PTV/RTV Not recommended 12 wks + RBV Not
recommended
SOF + SMV 12 wks, no RBV 12 wks, no RBV Not
recommended
SOF + DCV 12 wks, no RBV 12 wks, no RBV 12 wks, no RBV
EASL HCV Guidelines. April 2015.
*Recommendations the same for HCV-monoinfected and HCV/HIV-coinfected pts. †
8 wks may be used in
treatment-naive pts without cirrhosis if baseline HCV RNA < 6 million IU/mL, but should be done with
caution, especially in pts with F3 fibrosis.

EASL 2015 HCV*: Tx-Naive or PR-Exp’d,
GT1, 4, 5, or 6, Compensated Cirrhosis
*Recommendations the same for HCV-monoinfected and HCV/HIV-coinfected pts.
Regimen
HCV Genotype
1a 1b 4 5 or 6
SOF + PR 12 wks 12 wks 12 wks
SMV + PR 12 wks (naive or relapse)
12 wks (naive or relapse)
Not recommended
LDV/SOF 12 wks + RBV or 24 wks,
no RBV or 24 wks + RBV
if negative predictors
12 wks + RBV or 24 wks,
no RBV or 24 wks + RBV if
negative predictors
no RBV or 24 wks + RBV if
negative predictors
OBV/PTV/RTV
+ DSV
24 wks
+ RBV
12 wks
+ RBV
Not recommended Not recommended
OBV/PTV/RTV Not recommended 24 wks + RBV Not recommended
SOF + SMV 12 wks + RBV or 24 wks,
no RBV
no RBV
Not recommended
SOF + DCV 12 wks + RBV or 24 wks,
no RBV
no RBV
no RBV

EASL 2015 HCV*: Tx-Naive & PR-Exp’d,
GT2 or 3
Regimen
No Cirrhosis Compensated Cirrhosis
(Child-Pugh A)
GT2 GT3 GT2 GT3
SOF + PR 12 wks 12 wks 12 wks 12 wks
SOF + RBV†
12 wks 24 wks 16-20 wks Not
recommended
SOF + DCV 12 wks,
no RBV
12 wks,
no RBV
12 wks,
no RBV
24 wks
+ RBV
*Recommendations the same for HCV-monoinfected and HCV/HIV-coinfected pts.
†
Best first-line option for genotype 2 HCV; other options may be useful in pts with GT 2 HCV who
experience tx failure on sofosbuvir plus ribavirin. Suboptimal for genotype 3 HCV, particularly in pts with
cirrhosis and previous failure of PR.

OPTIMIST-1: SMV + SOF for 8 vs 12 Wks in
Noncirrhotic Tx-Naive & Tx-Exp’d GT1 Pts
 Multicenter, randomized, open-label phase III trial
– Key baseline characteristics: 75% GT1a (41% with Q80K), 73% IL28B
non-CC, 18% black, 15% Hispanic, 30% treatment experienced, median
HCV RNA: 6.83-6.85 log10 IU/mL
Kwo P, et al. EASL 2015. Abstract LP14.
Simeprevir 150 mg QD +
Sofosbuvir 400 mg QD
(n = 155)
(n = 155)
GT1 HCV–infected
noncirrhotic pts with
HCV RNA
> 10,000 IU/mL
(N = 310)
12 Wks8 Wks
OPTIMIST-1
Stratified by HCV subgenotype and Q80K in
GT1a; treatment history; IL28B GT
Historical
Control
97%†
83%*
87%
83%
*Not superior to historical control based on LL of 95% CI (76.3%) not > historical control rate.
†
Superior to historical control based on LL of 95% CI (93.7%) > historical control rate.
SVR12

OPTIMIST-1: SVR12 by Pt Subgroup
 Safety and tolerability consistent with previous reports
Kwo P, et al. EASL 2015. Abstract LP14.
SVR12(%)
100
80
60
40
20
0
SMV + SOF 12 wks SMV + SOF 8 wks
97
85
95
77
97
79
96
73
97
84
93
97 97 9796 96
84
77
100
92 92
64
112/
115
88/
103
38/
40
40/
52
112/
116
92/
116
44/
46
36/
49
68/
70
56/
67
38/
39
36/
39
43/
43
38/
41
83/
86
72/
86
24/
26
18/
28
54/
56
46/
48
96/
99
82/
107
n/N =
Naive Exp’d
Treatment
History
HCV GT
1a 1a +
Q80K
1a no
Q80K
1b
IL28B GT Baseline
HCV RNA
CC CT TT < 4 x 106
IU/mL
≥ 4 x 106
IU/mL

OPTIMIST-2: SMV + SOF for 12 Wks in
Cirrhotic Tx-Naive and Tx-Expd GT1 Pts
 Multicenter, open-label, single-arm phase III trial
– Key baseline characteristics: 70% GT1a (47% with Q80K), 72% IL28B
non-CC, 18% black, 16% Hispanic, 51% treatment exp'd, median HCV
RNA: 6.8 log10 IU/mL, 18% with platelets < 90,000 cells/mm3
, 51% with
albumin < 4 g/dL, 58% of 26 pts evaluated had FibroScan score > 20 kPa
– SVR12 compared with historical control, defined as 70% based on rates
with approved DAA + pegIFN/RBV regimens in relevant pt subgroups
– Superiority defined as LL of 95% CI for study treatment > historical control rate
Lawitz E, et al. EASL 2015. Abstract LP04.
(n = 103)
GT1 HCV–infected
pts with cirrhosis
and HCV RNA >
10,000 IU/mL
(N = 103)
12 Wks
OPTIMIST-2 Historical
Control
SVR12
83%* 70%
*Superior to historical control.

OPTIMIST-2: SVR12 by Pt Subgroup and
Safety Data
 Low rate of grade ≥ 3 AEs: 6%
 Majority of laboratory
abnormalities low grade
– Asymptomatic, transient
increases in bilirubin, amylase,
and lipase
SVR12 Rate
12 Wks of Simeprevir +
Sofosbuvir (n = 103)
% (n/N) 95% CI
Treatment history
 Naive 88 (44/50) 78.0-98.0
 Experienced 79 (42/53) 67.4-91.1
HCV subgenotype
 1a 83 (60/72) 74.0-92.6
 1a with Q80K 74 (25/34) 57.2-89.8
 1a without Q80K 92 (35/38) 82.2-100
 1b 84 (26/31) 69.3-98.4
IL28B genotype
 CC 86 (25/29) 71.9-100
 CT 85 (46/54) 74.8-95.6
 TT 79 (15/19) 58.0-99.9
Lawitz E, et al. EASL 2015. Abstract LP04.
SVR12 Rate
12 Wks of Simeprevir
+ Sofosbuvir (n = 103)
% (n/N) 95% CI
Platelet count
 < 90,000/mm3
68 (13/19) 44.9-92.0
 ≥ 90,000/mm3
87 (73/84) 79.1-94.7
FibroScan score
 > 20 kPa 80 (12/15) 56.4-100
 > 12.5 to 20 kPa 100 (11/11) 95.5-100

MALACHITE-II: OBV/PTV/RTV + DSV +
RBV vs TPV + PR in Tx-Expd GT1 Pts
 Multicenter, open-label, randomized phase III trial
– 6% with ≥ F3 fibrosis, 49% with null response to previous
pegIFN/RBV, 91% IL28B non-CC, 18% GT1a, 100% white race,
mean HCV RNA: 6.37-6.39 log10 IU/mL
Dore GJ, et al. EASL 2015. Abstract P0847.
Ombitasvir/Paritaprevir/Ritonavir
25 mg/150 mg/100 mg QD +
Dasabuvir 250 mg BID + RBV
(n = 101)
Telaprevir 750 mg every 8 hrs +
PegIFN/RBV
(n = 47)
GT1 HCV–
infected
noncirrhotic
pegIFN/RBV-
experienced pts
(N = 148)
12 Wks
PegIFN/RBV
24 or 48
Wks*
SVR12
99%
66%
P < .001
*PegIFN/RBV without TPV administered for additional 12-36 wks per local prescribing information.

75
9/
12
96
26/
27
MALACHITE-II: SVR12 by Subgroup
Dore GJ, et al. EASL 2015. Abstract P0847.
57
4/
7
75
9/
12
100
25/
25
57
13/
13
100
49/
49
100
19/
19
Ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV Telaprevir + pegIFN/RBV
1a Partial Null
100
80
60
40
20
0
SVR12(%)
Genotype
1b
Previous Response to PegIFN/RBV
68
27/
40
99
81/
82
Relapse
n/N =

MALACHITE-II: Pt-Reported SF-36v2
MCS/PCS and Laboratory Abnormalities
Dore GJ, et al. EASL 2015. Abstract P0847. Reproduced with permission.
Mental Component
Summary Score
Laboratory Abnormality, % OBV/PTV/RTV + DSV + RBV (n = 101) TPV + PegIFN/RBV (n = 47)
Hemoglobin 8 to < 10 g/dL 4 26
Hemoglobin < 8 g/dL 0 9
ALT > 5 x ULN 1 6
5
0
-5
-10
-15
-20
MeanChangeFrom
Baseline(95%CI)
B
L
W
4
W
8
W
12
W
16
W
24
W
36
W
48
PTW
4
PTW
12
Ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV TPV + pegIFN/RBV
5
0
-5
-10
-15
-20
B
L
W
4
W
8
W
12
W
16
W
24
W
36
W
48
PTW
4
PTW
12
Physical Component
Summary Score

GIFT-1: Ombitasvir/Paritaprevir/Ritonavir
for GT1b HCV
 International, part-randomized phase III trial conducted in Japanese pts
 Pts in Arms A and B more likely to be treatment-naive at baseline than those in Arm C
(65% and 64% vs 21%, respectively)
 Baseline BMI (all arms): 22.4-23.6
 Baseline IL28B CC: Arm A, 56%; Arm B, 51%; Arm C, 64%
(n = 215)
Placebo
(n = 106)
Noncirrhotic
pts with
GT1b HCV
(N = 321)
(n = 42)
Coformulated ombitasvir/paritaprevir/ritonavir dosed orally 25/150/100 mg once daily.
Cirrhotic
pts with
GT1b HCV
(N = 42)
(n = 106)
Arm A
Arm B
Arm C
Open label
Double-blind period
Wk 24Wk 12
Open-label period
Chayama K, et al. EASL 2015. Abstract G13. Reproduced with permission.

GIFT-1: Efficacy With 12 Wks
OBV/PTV/RTV in GT1b HCV
 SVR12 in patients with cirrhosis: 90.5% (38/42)
Chayama K, et al. EASL 2015. Abstract G13.
SVR12 in Noncirrhotic Pts,
% (n/N)
Immediate
All 94.9 (204/215)
Treatment-naive 94.2 (131/139)
Treatment-experienced 96.1 (73/76)

Management of Genotypes
2, 3, 4, and 5 HCV

BOSON: SOF + PegIFN/RBV for 12 Wks vs
SOF + RBV for 16 or 24 Wks in GT2/3 HCV
 Multicenter, randomized, open-label study
– Key baseline characteristics: 92% GT3, ~ 38% IL28B CC, ~ 53%
previously treated, ~ 37% with cirrhosis
Foster GR, et al. EASL 2015. Abstract LO5.
GT2 HCV–infected tx-
experienced pts with cirrhosis
and
GT3 HCV–infected tx-naive or
tx-experienced pts with or
without cirrhosis
(N = 592)
Sofosbuvir 400 mg QD + RBV*
(n = 196)
Sofosbuvir 400 mg QD + RBV*
(n = 199)
+ PegIFN†
+ RBV*
(n = 197)
Stratified by cirrhosis, HCV
GT, previous HCV tx
Wk 16Wk 12 Wk 24 SVR12, % (n/N)
GT2 GT3
87
(13/15)
71
(128/181)
100
(17/17)
84
(153/182)
94
(15/16)
93
(168/181)
*RBV: 1000-1200 mg/day. †
PegIFN alfa-2a: 180 μg/wk.

Treatment Naive Treatment Experienced
BOSON: SVR12 in GT3 by Tx History and
Cirrhosis Status
Foster GR, et al. EASL 2015. Abstract LO5. Reproduced with permission.
58/
70
65/
72
68/
71
12/
21
18/
22
21/
23
26/
34
17/
36
30/
35
44/
54
49/
52
41/
54
No Cirrhosis Cirrhosis No Cirrhosis Cirrhosis
83
90
96
57
82
91
76
82
94
47
77
86100
80
60
40
20
0
SVR12(%)
SOF + RBV 16 wks SOF + RBV 24 wks SOF + PegIFN/RBV 12 wks
n/N =

BOSON: Pts With SVR12 and
Safety/Tolerability
Foster GR, et al. EASL 2015. Abstract LO5. Reproduced with permission.
Outcome
16 Wks SOF +
RBV (n = 196)
24 Wks SOF +
RBV (n = 199)
12 Wks SOF +
PegIFN/RBV (n = 197)
On-treatment failure, n (%) 0 3 (2) 0
Relapse, n/N (%) 52/195 (27) 24/195 (12) 9/195 (5)
Other,* n (%) 3 (2) 2 (1) 5 (3)
Safety Outcome, n (%)
 Tx discontinuation for AE 3 (2) 2 (1) 1 (<1)
 Grade 3/4 lab abnormality 30 (15) 29 (15) 74 (38)
 Hemoglobin < 10 g/dL 7 (4) 12 (6) 24 (12)
 Hemoglobin < 8.5 g/dL 0 0 2 (1)
 Platelets < 50,000 cells/mm3
1 (1) 0 9 (5)
*Pts who discont. before achieving HCV RNA < LLOQ or did not return for Wk 12 posttreatment visit.

Ledipasvir/Sofosbuvir for 12 Wks in Pts
With GT4 or 5 HCV
 Open-label, single-arm study: 12 wks LDV/SOF 90/400
mg QD
 Tx naive or tx exp’d with GT4 or 5 HCV, cirrhosis
permitted
Abergel A, et al. EASL 2015. Abstract O056.
n/N =
SVR12, % (n/N) Genotype 4 Genotype 5
All 93 (41/44) 95 (39/41)
Treatment-naive 96 (21/22) 95 (20/21)
Treatment-experienced 91 (20/22) 95 (19/20)
Noncirrhotic 91 (31/34) 97 (31/32)
Cirrhotic 100 (10/10) 89 (8/9)

REGIMEN
GENOTIPO
1ª 1b 4 5
SOF +
LDV
- 12 Sem
- 8 sem naive- cirrosis
-RIV x 12 sem- cirrosis
compensated.
- 24 sem
contraindication for
RBV.
- without cirrhosis, treatment-naïve
and treatment-exp., for 12 weeks
without ribavirin.
- With cirrhosis adding RBV for 12
weeks.
-24 weeks RBV and treatment exp.
OBV/PTV/
RIV/ +
DSV
- Without cirrosis
+RIV for 12 weeks.
- With cirrosis + RIV
for 24 weeks.
- Without
cirrosis no RIV
for 12 weeks
- With cirrosis
+RIV.
- Without DSV
and adding RBV
for 12 or 24
weeks.
SOF +
SMV
- Without cirrhosis adding RIV
- With cirrosis for 24 weeks
- For 12 weeks.
- Adding RBV
with cirrosis.
- Contraindicati
ons for RBV,
24 weeks.
SOF +
DCV
- With cirrosis adding
RIV
- Cirrhosis
contraindications,
extendeng 24 weeks
- For 12 weeks
- + RBV with cirrosis.
- 24 weeks in contraindications for
RBV.

REGIMEN GT 2 GT 3
SF + RV - 12 weeks without cirrosis
- 20-24 weeks with cirrhosis
- For 24 weeks
SF + PEG/RV - 12 weeks with cirrosis/
treatment exp.
+
SF + DCV - 12 weeks with
cirrosis/treatment exp.
+

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