In this downloadable slideset, Mark S. Sulkowski, MD, discusses key practice-changing data from the 2015 liver disease meeting in Vienna.
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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
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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.
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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.
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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
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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.
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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
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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
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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 =
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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
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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
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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
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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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