HCV Alerts- Rapid Response to Practice-Changing Advances From EASL 2015

HCV Alerts: Rapid Response to
Practice-Changing Advances
Supported by an educational grant from AbbVie.

Practice-Changing Advances
From EASL 2015

clinicaloptions.com/hepatitis
HCV Alerts: Rapid Response to Practice-Changing Advances
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Faculty
Mark S. Sulkowski, MD
Professor of Medicine
Medical Director, Viral Hepatitis
Center
Divisions of Infectious Diseases
and
Gastroenterology/Hepatology
Johns Hopkins University
School of Medicine
Baltimore, Maryland
Program Director:
Paul Y. Kwo, MD
Professor of Medicine
Medical Director of
Transplantation
Division of Medicine/
Gastroenterology/Hepatology
Indiana University School of
Medicine
Indianapolis, Indiana

Faculty Disclosures
Mark S. Sulkowski, MD, has disclosed that he has received
consulting fees from AbbVie, Achillion, Bristol Myers Squibb,‐
Gilead Sciences, Janssen, and Merck; funds for research
support from AbbVie, Bristol Myers Squibb, Gilead Sciences,‐
and Merck; and data and safety monitoring board funding (to
his institution) from Gilead Sciences.
Paul Y. Kwo, MD, has disclosed that he has received funds
for research support from AbbVie, Bristol-Myers Squibb,
Conatus, Gilead Sciences, Janssen, Merck, and Roche and
consulting fees from AbbVie, Bristol-Myers Squibb, Gilead
Sciences, Janssen, and Merck.

Managing HCV Infection
in Renal Disease

RUBY-1: OMV/PTV/RTV + DSV ± RBV in
Tx-Naive, Noncirrhotic GT1 Pts With CKD
 Interim analysis of multicenter, open-label phase IIIb study
 Ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + dasabuvir
250 mg BID ± ribavirin* 200 mg QD for 12 wks
 Key baseline characteristics
– F2 fibrosis: 30%; F3 fibrosis: 20%
– CKD stage 4 (eGFR 15-30): 35%; CKD stage 5 (eGFR < 15): 65%
– 65% of pts on hemodialysis
Pockros PJ, et al. EASL 2015. Abstract L01.
*RBV dosed 4 hrs before hemodialysis in hemodialysis pts; weekly hemoglobin assessment in Month 1
and then Wks 6, 8, 12; RBV suspended in pts with > 2 g/dL decline in hemoglobin in < 4 wks or
hemoglobin < 10 g/dL; RBV dosing resumed at clinician’s discretion if hemoglobin normalized.

RUBY-1: Safety and Interim Efficacy
 OMV/PTV/RTV + DSV ± RBV well tolerated for GT1 HCV and advanced CKD
 No treatment-related serious AEs,
discontinuations, or significant
changes in liver or renal function
to date
 RBV dose interruption in 8/13
GT1a pts (6 in first 4 wks)
– 4 pts received EPO, 1 pt with
hemoglobin < 8 mg/dL
 Most AEs mild to moderate
 Interim virologic efficacy
– SVR4 in 10/10 pts reaching posttreatment Wk 4
– SVR12 in 2/2 pts reaching posttreatment Wk 12
– No virologic failures observed as of time of reporting
Pockros PJ, et al. EASL 2015. Abstract L01.
AEs Found
in > 3 Pts,
n
GT1b:
OMV/PTV/RTV
+ DSV
(n = 7)
GT1a:
OMV/PTV/RTV
+ DSV + RBV
(n = 13)
Anemia 0 8
Fatigue 2 4
Diarrhea 1 4
Nausea 0 5

Saxena V, et al. EASL 2015. Abstract LP08.
HCV TARGET: Similar SVR12 Rates With
SOF Regimens Regardless of eGFR
 Longitudinal observational study in 1893 sequentially enrolled pts
– Sofosbuvir + simeprevir the most common regimen used
 Overall SVR12 rates high and similar (> 80%) across renal function
strata in pts with known treatment outcome
81
48
88
17
≤ 30*
100
80
60
40
20
0
SVR12(%)
eGFR
81
1393
89
140
31-45 46-60 > 60
N =
*Sofosbuvir use with eGFR
< 30 mL/min/1.73m2
is off label.

HCV TARGET: Rates of Anemia/Renal AEs
Inversely Related to Baseline eGFR
Outcome in Pts Completing SOF-
Containing Therapy ± RBV, % (n)
eGFR ≤ 30
(n = 17)
eGFR 31-45
(n = 56)
eGFR 46-60
(n = 157)
eGFR > 60
(n = 1559)
Anemia AEs 35 (6) 29 (16) 24 (37) 16 (246)
 Transfusions 12 (2) 9 (5) 2 (3) 2 (31)
 Erythropoietin 6 (1) 14 (8) 9 (14) 3 (50)
 RBV dose reduction* 38 (3) 30 (8) 42 (33) 19 (185)
 RBV discontinuation* 0 15 (4) 1 (1) 1 (12)
Worsening renal function 29 (5) 11 (6) 3 (4) 1 (14)
Renal or urinary AEs 29 (5) 11 (6) 8 (13) 5 (84)
Serious AEs 18 (3) 23 (13) 5 (8) 6 (100)
Cardiac AEs 6 (1) 4 (2) 5 (8) 3 (53)
Saxena V, et al. EASL 2015. Abstract LP08.
*Among pts who received RBV

Take-Home Points: HCV Therapy in the
Setting of Renal Insufficiency
 Safety and efficacy data now available for OMV/PTV/RTV
+ DSV ± RBV in hemodialysis pts
– In pts with genotype 1a HCV, AEs remain a concern with
RBV, even at low doses
 Efficacy data now for available for SOF-based regimens in
pts with eGFR ≤ 30
– Owing to decreased excretion of metabolite GS-331007,
safety remains uncertain

Role of Resistance Testing in HCV
Retreatment

24 Wks of LDV/SOF After Failure of 8-12
Wks of LDV/SOF-Based Therapy in GT1 Pts
 Results from single arm of prospective phase II trial
 NS5B variants with resistance to SOF emerged during retreatment in 33% of
pts (4/12) with virologic failure
– S282T: n = 3 (out of 12)
Lawitz E, et al. EASL 2015. Abstract O005.
LDV/SOF 90/400 mg QD
GT1 HCV–infected
pts previously treated with
LDV/SOF-based therapy
(N = 41)
24 Wks
100
80
60
40
20
0
SVR12(%)
All No Yes
71 68
74
15/
22
14/
19
No Yes8 Wks 12 Wks
Cirrhosis Previous Tx
Duration
BL NS5A RAVs
80
46
60
100
24/
30
5/
11
11/
11
18/
30n/N =
29/
41

OPTIMIST-2: SMV + SOF for 12 Wks in
Cirrhotic Tx-Naive and Tx-Exp’d GT1 Pts
 Multicenter, open-label, single-arm
phase III trial[1]
 Key baseline characteristics
– 70% GT1a (47% with Q80K)
– 72% IL28B non-CC
– 18% black, 16% Hispanic
– 51% treatment exp’d
– 18% with platelets
< 90,000 cells/mm3
– 51% with albumin < 4 g/dL
 Among cirrhotic pts, SVR12 rates
were lower in those with GT1a with
Q80K mutation
 OPTIMIST-1: No impact of Q80K
seen in noncirrhotic pts with GT1a[2]
1. Lawitz E, et al. EASL 2015. Abstract LP04. 2. Kwo P, et al. EASL 2015. Abstract LB14.
100
80
60
40
20
0
SVR12(%)
GT1a GT1a
With
Q80K
GT1a
Without
Q80K
GT1b
60/72 25/34 35/38 26/31
83
74
92
84
n/N =

Take-Home Points: Role of Resistance
Testing
 The presence of resistance associated variants to DAAs
prior to treatment may have an impact on SVR, especially
in pts with previous DAA treatment experience and/or
cirrhosis
 Consider resistance testing prior to retreatment in patients
who fail to achieve HCV cure with DAA-based treatments

Advances in the Treatment of
Genotype 3 HCV Infection

Treatment Naive Treatment Experienced
BOSON: SVR12 in GT3 by Tx History and
Cirrhosis Status
Foster GR, et al. EASL 2015. Abstract LO5.
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 for 16 wks SOF + RBV for 24 wks SOF + pegIFN/RBV for 12 wks
n/N =
 Multicenter, randomized, open-label study

BOSON: SOF + RBV + PegIFN for 12 Wks
Was Safe and Well Tolerated
Foster GR, et al. EASL 2015. Abstract LO5.
Safety Outcome, % (n)
16 Wks of
SOF + RBV
(n = 196)
24 Wks of
SOF + RBV
(n = 199)
12 Wks of SOF +
PegIFN/RBV
(n = 197)
AEs 94 (185) 95 (188) 99 (195)
Grade 3/4 AEs 6 (11) 4 (7) 8 (15)
Serious AEs 4 (8) 5 (10) 6 (12)
Treatment discontinuation for AEs 2 (3) 1 (2) <1 (1)
Laboratory abnormalities
 Grade 3/4 15 (30) 15 (29) 38 (74)
 Hemoglobin < 10 g/dL 4 (7) 6 (12) 12 (24)
 Hemoglobin < 8.5 g/dL 0 0 1 (2)
 Platelets < 50,000 cells/mm3
<1 (1) 0 5 (9)
 Low rates of serious AEs, laboratory abnormalities, and treatment
discontinuations due to AEs

Take-Home Points: Treatment for
Genotype 3 HCV Infection
 SOF + pegIFN/RBV for 12 wks may be best current option
in treatment-experienced pts with GT3 HCV infection
– Addition of pegIFN to SOF + RBV for 12 wks associated with
highest rate of SVR12 in treatment-experienced pts with
GT3, particularly those with cirrhosis
 To achieve high SVR rates with SOF in GT3, an additional
active drug may be needed
– Studies of combinations of novel DAAs with increased
activity against GT3 are under way

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HCV Alerts- Rapid Response to Practice-Changing Advances From EASL 2015

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