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/hepatitisHCV Approved Therapies

April 22-26, 2015Vienna, Austria

Highlights From EASL:HCV Approved TherapiesCCO 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 fromAbbVie, Gilead Sciences, and Merck.

2015 EASL HCV Guidelines


EASL 2015 HCV*: Tx-Naive or PR-Exp’d, GT1, 4, 5, or 6, Without Cirrhosis

RegimenHCV 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)24 wks (partial/null)

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.

RegimenHCV 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)24 wks (partial/null)

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

12 wks + RBV or 24 wks, 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

12 wks + RBV or 24 wks, no RBV

Not recommended

SOF + DCV 12 wks + RBV or 24 wks, 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.

Management of Genotype 1 HCV


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 WksOPTIMIST-1Stratified by HCV subgenotype and Q80K in

GT1a; treatment history; IL28B GTHistorical 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.

SV

R12

(%

)

100

80

60

40

20

0

SMV + SOF 12 wks SMV + SOF 8 wks

9785

95

77

97

79

96

73

97

84

9397 97 9796 96

8477

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 Rate12 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 Rate12 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

SV

R12

(%

)

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

Mea

n C

ha

ng

e F

rom

B

asel

ine

(95%

CI)

BLW

4W

8W

12W

16W

24W

36W

48

PTW4

PTW12

Ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV TPV + pegIFN/RBV

5

0

-5

-10

-15

-20

BLW

4W

8W

12W

16W

24W

36W

48

PTW4

PTW12

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%

Ombitasvir/Paritaprevir/Ritonavir (n = 215)

Placebo(n = 106)

Noncirrhotic pts with

GT1b HCV (N = 321)


Coformulated ombitasvir/paritaprevir/ritonavir dosed orally 25/150/100 mg once daily.

Cirrhotic pts with

GT1b HCV(N = 42)


Arm A

Arm B

Arm C

Open label

Double-blind periodWk 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

andGT3 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)

Sofosbuvir 400 mg QD + 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

8390

96

57

8291

7682

94

47

7786100

80

60

40

20

0

SV

R12

(%

)

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.

Outcome16 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)


REGIMENGENOTIPO

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.

+

GRACIAS…

Date post:	07-Aug-2015
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