Transcript Clinical Updates in HCV Treatment CCO Independent

Clinical Updates in HCV Treatment
CCO Independent Conference Coverage
of the 2007 Annual Meeting of the European Association for the Study of the Liver*
April 11-15, 2007
Barcelona, Spain
*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 an educational grant from
EASL 2007: Clinical Updates in HCV Treatment
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diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without
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clinicaloptions.com/hep
Novel Protease Inhibitors for
Hepatitis C
EASL 2007: Clinical Updates in HCV Treatment
PROVE 1: Telaprevir + Peg-IFN/RBV in
Treatment-Naive HCV GT 1 Patients

Current analysis: data on all patients through Week 12 of treatment
– Also patients in 12-week treatment arm who made it to Week 20 of follow-up
Week 12: Interim Analysis
Randomized,
phase II trial
*
(N = 260
planned)
Placebo
+ Peg-IFN alfa-2a + RBV
(n = 80)
Telaprevir 750 mg every 8 hrs
+ Peg-IFN alfa-2a + RBV
(n = 80)
Telaprevir 750 mg every 8 hrs
+ Peg-IFN alfa-2a + RBV
(n = 80)
Telaprevir 750 mg every 8 hrs
+ Peg-IFN alfa-2a + RBV
(n = 20)
Week 24
Week 48
24-Week
Peg-IFN alfa-2a + RBV
(n = 80)
Follow-up
24-Week
Peg-IFN alfa-2a + RBV
(n = 80)
Peg-IFN alfa-2a
+ RBV
(n = 80)
†
†
Week 72
Follow-up
24-Week
Follow-up
24-Week
Follow-up
*Patients received telaprevir 1250-mg loading dose or placebo based on the arm to which they were randomized. †Patients
must achieve undetectable HCV RNA at Week 4 (< 10 IU/mL) and at last test before stopping therapy at 12 or 24 weeks.
McHutchison JG, et al. EASL 2007. Late Breaker 786.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
PROVE 1: Telaprevir + Peg-IFN/RBV in
Treatment-Naive HCV GT 1 Patients
 High rates of RVR (Week 4)
and EVR (Week 12)
Virologic Response Rates
(HCV RNA < 10 IU/mL)
Telaprevir + peg-IFN + RBV
(pooled; n = 175 dosed)
 Virologic breakthrough rates
Peg-IFN + RBV (n = 75 dosed)
– Telaprevir: 7% (12/175)
– Controls: 3% (2/80)
– 67% (6/9) patients who
achieved Week 4 RVR and
discontinued treatment after 12
weeks were HCV RNA negative
20 weeks posttreatment
80
Patients (%)
 Follow-up for 12-week
treatment arm
100
P < .001
79
70
60
39
40
20
11
0
Week 4
McHutchison JG, et al. EASL 2007. Late Breaker 786.
P < .001
Week 12
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
PROVE 1: Telaprevir + Peg-IFN/RBV in
Treatment-Naive HCV GT 1 Patients
 Discontinuation due to adverse events through Week 12
– Control arm: n = 2 (3%)
– Telaprevir: n = 19 (11%)
– Rash most common cause for telaprevir discontinuation (n = 7)
– Median time to onset of severe rash: 62 days
Adverse Event, %
Telaprevir + Peg-IFN + RBV
(Pooled; n = 175)
Peg-IFN + RBV
(n = 75)
Severe rash
6
0
Nausea
50
30
 Severe
2
2
Pruritus
37
20
Diarrhea
34
21
Grade 1 anemia
40
29
Grade 2 anemia
17
9
McHutchison JG, et al. EASL 2007. Late Breaker 786.
clinicaloptions.com/hep
Novel Polymerase Inhibitors
for Hepatitis C
EASL 2007: Clinical Updates in HCV Treatment
Valopicitabine in Treatment-Naive HCV
Genotype 1 Patients
Week 1
No TX
Treatmentnaive
patients with
HCV GT 1
(N = 172*)
Valopicitabine
200 mg/day
Valopicitabine
ramped from
400-800 mg/day
Valopicitabine
800 mg/day
Week 4
Peg-IFN
alfa-2a
alone
Week 12-22
Study Amendment*
Week 48
Peg-IFN alfa-2a 180 µg/week +
Valopicitabine 800 mg/day
(n = 34)
Peg-IFN alfa-2a 180 µg/week +
Valopicitabine 200 mg/day
(n = 34)
Peg-IFN alfa-2a 180 µg/week +
Valopicitabine 800 mg/day
(n = 34)
Peg-IFN alfa-2a 180 µg/week +
Valopicitabine 800 mg/day
(n = 36)
Week 72
24-Week
Follow-up
Peg-IFN alfa-2a 180 µg/week + Valopicitabine 800 mg/day
(n = 35)
*Week 12 GI-related adverse events resulted in reduction of valopicitabine dose in arms receiving 800 mg;
these patients were randomly reassigned 1:1 to valopicitabine 200 mg or 400 mg + peg-IFN for the
remainder.
Lawitz E, et al. EASL 2007. Abstract 14.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Valopicitabine in Treatment-Naive HCV
Genotype 1 Patients (cont’d)
 800-mg groups pooled for efficacy analysis
 Mean HCV RNA decrease at Week 48
– Valopicitabine 200 mg + peg-IFN alfa-2a: -4.02 IU/mL
– Valopicitabine 800 mg + peg-IFN alfa-2: -3.94 IU/mL
Proportion of Patients With Undetectable HCV RNA (< 20 IU/mL)*
Patients (%)
100
80
60
62
44
50
47
40
53
38
Valopicitabine 800 mg +
peg-IFN alfa-2a (n = 139)
20
0
Valopicitabine 200 mg +
peg-IFN alfa-2a (n = 34)
Week 12
Week 24
*Dropout = treatment failure.
Lawitz E, et al. EASL 2007. Abstract 14.
Week 48
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Valopicitabine in Treatment-Naive HCV
Genotype 1 Patients (cont’d)

Discontinuation rates, adverse events tended to be higher with 800-mg dose
– 7 treatment-related serious adverse events

Incidence of valopicitabine-related GI adverse events dose dependent
Outcome, %
Valopicitabine 200 mg +
Peg-IFN alfa-2a (n = 34)
Valopicitabine 800 mg +
Peg-IFN alfa-2a (n = 139)
Treatment discontinuation
38
55
Diarrhea
38
44
Nausea
65
81
Vomiting
38
53
Headache
27
30
Fatigue
44
50
Depression
21
23
Flu-like symptoms
18
29
Lawitz E, et al. EASL 2007. Abstract 14.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Retreatment With Valopicitabine in
HCV Nonresponders to Peg-IFN/RBV
 Phase IIb study of valopicitabine ± peginterferon
Week 1
(n = 21)
GT 1 previous
nonresponders with
HCV RNA ≥ 105 IU/mL,
ALT < 5 x ULN, and
compensated liver
disease
(N = 190)
Week 48
Week 72
Valopicitabine 800 mg/day monotherapy
(n = 42)
Val
400 mg/day
(n = 42)
Val 400 →
800 mg/day
Peg-IFN + Valopicitabine 800 mg*
(n = 42)
Val
800 mg/day
Peg-IFN + Valopicitabine 800 mg*
(n = 43) No Treatment
Peg-IFN + Valopicitabine 400 mg/day
Follow-up
Peg-IFN + RBV 1000-1200 mg
*Data pooled from two 800-mg groups in current analysis.
Afdhal NH, et al. EASL 2007. Abstract 6.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Retreatment With Valopicitabine in
HCV Nonresponders to Peg-IFN/RBV
Peg-IFN + RBV
Valopicitabine 400 mg/day
+ Peg-IFN
Week 48 Mean Reduction in HCV RNA
0
Valopicitabine 800 mg/day
+ Peg-IFN (pooled data)
Virologic Response Rates (< 50 IU/mL)
100
80
-1.0
Patients (%)
Mean log10 Change
-0.5
-1.5
-2.0
-2.5
-2.29
-2.23
40
24
20
15
20
3
-3.0
-3.5
60
0
0
0
-3.11
Afdhal NH, et al. EASL 2007. Abstract 6.
Week 48
SVR
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Retreatment With Valopicitabine in
HCV Nonresponders to Peg-IFN/RBV
Outcome, %
Discontinued treatment
 Due to adverse event
Nausea
Fatigue
Vomiting
Diarrhea
Headache
Depression
Insomnia
Neutropenia
Valopicitabine
800 mg/day +
Peg-IFN
(n = 82)
78
23
82
56
66
49
39
28
27
24
Afdhal NH, et al. EASL 2007. Abstract 6.
Valopicitabine
400 mg/day +
Peg-IFN
(n = 41)
88
20
73
51
49
32
42
10
10
29
Peg-IFN +
RBV
(n = 34)
85
3
35
68
9
15
27
29
29
12
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
HCV-796 + Peg-IFN in Treatment-Naive
Hepatitis C Patients
Day 1:
Peg-IFN Dose 1
Day 7:
Peg-IFN Dose 2
Day 14:
End of Treatment
Placebo +
Peginterferon alfa-2b 1.5 µg/kg
(n = 19)
Treatment-naive chronic
hepatitis C patients
without advanced or
decompensated liver
disease
(N = 65)
HCV-796 100 mg BID +
Peginterferon alfa-2b 1.5 µg/kg
(n = 12)
HCV-796 250 mg BID +
Peginterferon alfa-2b 1.5 µg/kg
(n = 10)
Day 28
Follow-up
HCV-796 500 mg BID +
Peginterferon alfa-2b 1.5 µg/kg
(n = 12)
HCV-796 1000 mg BID +
Peginterferon alfa-2b 1.5 µg/kg
(n = 12)
Villano SA, et al. EASL 2007. Abstract 50.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
HCV-796 in Treatment-Naive
Hepatitis C Patients
Day 14 Change in HCV RNA From Baseline
100
92
78
Patients (%)
80
70
Peg-IFN (n = 15)
70 67 67 70
70
100 mg HCV-796
+ Peg-IFN (n = 10)
60
40
40
33 33 30
20
20
13
13
0
≥ 2 Log Change
≥ 3 Log Change
HCV RNA Negative*
250 mg HCV-796
+ Peg-IFN (n = 9)
500 mg HCV-796
+ Peg-IFN (n = 10)
1000 mg HCV-796
+ Peg-IFN (n = 12)
*< 50 IU/mL.
Villano SA, et al. EASL 2007. Abstract 50.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
HCV-796 in Treatment-Naive
Hepatitis C Patients (cont’d)
Mean log10 Change: Day 14
1
0
-1
-2
-3
-4
Genotype 1
-5
Villano SA, et al. EASL 2007. Abstract 50.
Genotype Non-1
clinicaloptions.com/hep
Novel Small Molecule Therapies
for Hepatitis C
EASL 2007: Clinical Updates in HCV Treatment
Efficacy of DEBIO-025 in
HIV/HCV-Coinfected Patients
 DEBIO-025: oral small
molecule inhibitor of
cyclophilin
 Biphasic viral decay kinetics
demonstrated
8
7
6
5
4
3
2
1
Treatment
 Effective across GT 1, 3, 4
 No rebounds noted
Herrmann E, et al. EASL 2007. Abstract 88.
Placebo
9
HCV RNA
(log10 copies/mL)
 1200 mg twice daily for
14 days (n = 16) vs placebo
(n = 3) in treatment-naive
HIV/HCV-coinfected patients
DEBIO-025
-28
0
10
20
30
Time (Days)
40
50
Figure used with permission from Dr. Eva Herrmann.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
NS4A Antagonist ACH-806 in HCV
Genotype 1–Infected Patients

ACH-806 300 mg twice daily for 5 days (n = 8) vs placebo (n = 2) in naive or
experienced patients
ACH-806 (n = 8)
Placebo (n = 2)
Mean Change in HCV
RNA log10 (IU/mL)
0.2
0
-0.2
-0.4
-0.6
-0.8
Treatment
-1.0
0
2
4
6
8
10
12
Study Day
14
16
18
20
Figure used with permission from John C. Pottage, Jr., MD.
Pottage JC, et al. EASL 2007. Abstract 783.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
NS4A Antagonist ACH-806 in HCV
Genotype 1–Infected Patients (cont’d)
 4 patients had > 1 log10 IU/mL reduction in HCV RNA
– Mean reduction: 0.91 log10 IU/mL
 6 individuals had increases in serum creatinine
– Mean Day 3 increase: 0.43 mg/dL
– Mean Day 5 increase: 0.49 mg/dL
 Drug development halted due to renal toxicity
 Proof of concept demonstrated
Pottage JC, et al. EASL 2007. Abstract 783.
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Novel Interferons for Hepatitis C
EASL 2007: Clinical Updates in HCV Treatment
Albinterferon Alfa-2b/RBV Treatment in
Genotype 2/3 Patients

Interim analysis of multicenter, randomized, open-label, phase II trial
– Albinterferon alfa-2b recombinant interferon fused with human serum albumin
Stratification by
HCV genotype (2 or 3) and
HCV RNA (< vs ≥ 800,000 IU/mL)
Treatment-naive
patients chronically
infected with HCV
genotype 2/3
(N = 43)
Week 24
Albinterferon alfa-2b 1500 µg
every 2 weeks subcutaneously +
Ribavirin 800 mg/day
(n = 21)
Albinterferon alfa-2b 1500 µg
every 4 weeks subcutaneously +
Ribavirin 800 mg/day
(n = 22)
Bain VG, et al. EASL 2007. Abstract 9.
Follow-up planned
for 24 additional
weeks; interim
follow-up performed
at Week 36
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Albinterferon Alfa-2b/RBV Treatment in
Genotype 2/3 Patients (cont’d)
Alb-IFN Q4W + RBV (n = 22)
Week 36 Outcomes
According to Genotype
Undetectable HCV RNA (%)
Virologic Outcomes
95.5
100
85.7
80 76.2
95.5
85.7
68.2
66.7
72.7
60
40
20
0
24†
Week 4* Week 12* Week
(EOT)
*Limit of detection, 43 IU/mL.
†Limit of detection, 10 IU/mL.
Bain VG, et al. EASL 2007. Abstract 9.
36†
Week
(Post-Tx)
Undetectable HCV RNA (%)
Alb-IFN Q2W + RBV (n = 21)
100
80
60
83.3
80.0
60.0
54.5
40
20
0
GT 2†
GT 3†
Figures used with permission from
Vincent G. Bain, MD, FRCP(C).
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Albinterferon-Based Therapy vs
Standard of Care
Stratification by HCV RNA
(< vs ≥ 800,000 copies/mL) and
body mass index (< vs ≥ 25)
Week 60:
Current Interim
Analysis
Week 48
Week 72
Albinterferon alfa-2b 900 µg Q2W +
Weight-Based Ribavirin 1000-1200 mg/day
(n = 118)
Interferon-naive,
genotype 1,
chronic hepatitis C
patients
(N = 458)
Albinterferon alfa-2b 1200 µg Q2W +
Weight-Based Ribavirin 1000-1200 mg/day
(n = 110)
Albinterferon alfa-2b 1200 µg Q4W +
Weight-Based Ribavirin 1000-1200 mg/day
(n = 116)
24-Week
Follow-up
Peginterferon alfa-2a 180 µg/week +
Weight-Based Ribavirin 1000-1200 mg/day
(n = 114)
Zeuzem S, et al. EASL 2007. Abstract 779.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Albinterferon-Based Therapy vs
Standard of Care (cont’d)
Proportion of Patients With Undetectable HCV RNA
100
Patients (%)
80
70
60
80
78
70
59 56
53 54
34
18
Week 4*
*< 43 IU/mL.
†< 10 IU/mL.
Alb-IFN 900 μg Q2W
Alb-IFN 1200 μg Q2W
26
25
0
66
73
53
40
20
75
Alb-IFN 1200 μg Q4W
Peg-IFN 180 µg/week
Week 12*
End of
Week 12
†
Treatment Posttreatment†
Figure used with permission from Stefan Zeuzem, MD.
Zeuzem S, et al. EASL 2007. Abstract 779.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Albinterferon-Based Therapy vs
Standard of Care (cont’d)
 Quality of life significantly less impaired for patients on
albinterferon 1200 µg every 4 weeks vs those on
peginterferon at Weeks 12, 24, and 48 (P < .05)
Safety and Dose
Reductions, %
Alb-IFN 900 µg
Q2W + RBV
(n = 118)
Alb-IFN 1200 µg
Q2W + RBV
(n = 110)
Alb-IFN 1200 µg
Q4W + RBV
(n = 116)
Peg-IFN 180 µg
Q1W + RBV
(n = 114)
Severe adverse events
31.4
40.9
29.3
27.2
Treatment discontinuation
due to adverse event
9.3
19.1
12.1
6.1
Interferon dose reduction
29.7
33.6
10.3
28.1
 Due to adverse event
4.2
7.3
3.4
8.8
 Due to lab abnormality
25.4
27.3
6.0
22.8
Zeuzem S, et al. EASL 2007. Abstract 779.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Recombinant IFN Omega for
Treatment-Naive GT 1 Patients
 Randomized, open-label, phase II trial
Week 12:
Subjects must demonstrate
a > 2 log10 reduction in HCV RNA
level* to continue
Interferon Omega
25 µg/day
(n = 35)
Treatment-naive patients
with genotype 1
chronic HCV infection
(N = 102)
Week 48:
ETR
Week 72:
SVR
Follow-up
Interferon Omega 25 µg/day +
Ribavirin 1000/1200 mg BID
(n = 67)
*Limit of detection < 600 IU/mL.
Novozhenov V, et al. EASL 2007. Abstract 11.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Recombinant IFN Omega for
Treatment-Naive GT 1 Patients (cont’d)
Virologic Response Rates
Omega alone (n = 35)
100
P = .014
84
Patients (%)
Omega + ribavirin (n = 67)
78
75
60
54
P = .001
50
36
25
36
17
6
0
EVR
HCV RNA- Week 12
Novozhenov V, et al. EASL 2007. Abstract 11.
ETR
SVR
clinicaloptions.com/hep
Ribavirin Analogues for
Hepatitis C
EASL 2007: Clinical Updates in HCV Treatment
VISER 2: Efficacy of Taribavirin vs
Ribavirin in Hepatitis C
 Multicenter, active-control, parallel group, double-blind
phase III study
2:1
Randomization
Treatment-naive chronic
hepatitis C patients
(N = 962)
24 or 48 Weeks
of Treatment*
Taribavirin 600 mg BID +
Peginterferon alfa
(n = 644)
Ribavirin 1000/1200 mg BID +
Peginterferon alfa
(n = 318)
24 Weeks of
Follow-up
*According to genotype.
Marcellin P, et al. EASL 2007. Abstract 10.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
VISER 2: Efficacy of Taribavirin vs
Ribavirin in Hepatitis C (cont’d)
SVR Rate*, %
Overall
Genotype 1 patients
Genotype 2/3 patients
Ribavirin +
Peginterferon
(n = 318)
55
44
81
Taribavirin +
Peginterferon
(n = 644)
40
27
67
*HCV RNA < 39 IU/mL.
Marcellin P, et al. EASL 2007. Abstract 10.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
VISER 2: Efficacy of Taribavirin vs
Ribavirin in Hepatitis C (cont’d)
 Higher rate of anemia in ribavirin vs taribavirin group
– 22% vs 6%, respectively (P < .001)
 Post hoc subgroup analysis: higher SVR rates in those
receiving > 15 mg/kg taribavirin
– Increase in anemia rate in those receiving > 15 mg/kg of
taribavirin
Ribavirin
Taribavirin Dose, mg/kg
≤ 13
> 13-15
> 15-18
> 18
Patients, n
318
171
164
190
119
SVR, %
55
26
42
47
48
Anemia, %
22
4
2
8
13
Marcellin P, et al. EASL 2007. Abstract 10.
clinicaloptions.com/hep
Using Virologic Response to
Determine Treatment Duration
EASL 2007: Clinical Updates in HCV Treatment
Extended Treatment in Genotype 1
Slow Responder Patients
Week 8
Week 24
Week 48
Week 72
Week 96
Treatment
length
determined
Standard Tx
regardless of
response
Treatment-naive
patients with
HCV GT 1
infection
(N = 694)
HCV RNA
negative at
Week 4
HCV RNA
negative at
Week 8
Peg-IFN + RBV for 48 weeks
(n = 235)
Peg-IFN + RBV
for 24 weeks
(n = 122)
Follow-up
Peg-IFN + RBV for 48 weeks
(n = 128)
HCV RNA
positive at
Week 8
Mangia A, et al. EASL 2007. Abstract 7.
Follow-up
Follow-up
Peg-IFN + RBV for 72 weeks
(n = 52)
Follow-up
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Extended Treatment in Genotype 1
Slow Responder Patients (cont’d)
Virologic Outcomes in Week 12 Responders (< 50 IU/mL)
48-week treatment
72-week treatment
100
77
Patients (%)
80
P = .06
68
63
60
37
40
20
0
End of Treatment
Response
Mangia A, et al. EASL 2007. Abstract 7.
SVR
clinicaloptions.com/hep
Predictors of SVR
EASL 2007: Clinical Updates in HCV Treatment
Week 4 Ribavirin Concentration as a
Predictor of SVR

Week 4 ribavirin concentrations correlated with SVR in 22 patients
– Cutoff of 2 mg/L significantly associated with SVR
P = .03
P = .05
100
80
60
50
40
33
20
20
0
86
80
SVR Rate* (%)
SVR Rate* (%)
100
n=
6
5
< 1.51
6
1.51-1.73 1.74-2.43
Week 4 Ribavirin (mg/L)
5
> 2.43
80
60
40
27
20
0
n=
7
15
≤2
>2
Week 4 Ribavirin (mg/L)
*Measured through quantitative PCR.
Maynard M, et al. EASL 2007. Abstract 619.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Relationship Between Renal Function
and SVR in Hepatitis C Patients
 German multicenter, open-label, observational study
 Treatment-naive HCV patients (N = 10,326) screened
– Initiated peginterferon plus ribavirin with complete GFR data sets
(n = 1615)
– Patients stratified into 2 groups
– Normal GFR: > 90 mL/min/1.73 m2 (n = 1498)
– Low GFR: 60-90 mL/min/1.73 m2 (n = 107)
– 10 patients with GFR < 60 mL/min/1.73 m2 excluded from analysis
 GFR differed according to sex, age, and HCV genotype but not
according to weight or BMI
Zehnter E, et al. EASL 2007. Abstract 656.
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Relationship Between Renal Function
and SVR in Hepatitis C Patients (cont’d)


GFR affected response rates in genotype 1,4 but not genotype 2,3 patients
Anemia more common among patients with low GFR
Normal GFR (> 90; n = 1498)
100
75.0
61.4
60
49.7
41.1
40
33.3
20
60
35.5
40
16.1
20
n=
0
80
Patients (%)
76.0
Anemia
100
Sustained Virologic Response
80
Patients (%)
Low GFR (> 60-90; n = 107)
920
413
Total
44
29
Genotype 1/4
507
15
Genotype 2/3
Figures used with permission from Elmar Zehnter, MD.
Zehnter E, et al. EASL 2007. Abstract 656.
n=
0
241
38
Total
clinicaloptions.com/hep
Summary and Conclusions
EASL 2007: Clinical Updates in HCV Treatment
Conclusions
Protease inhibitors
 High rates of rapid response with telaprevir plus peginterferon/ribavirin
in naive patients based on interim data
– High sustained response rates in those undergoing 12 weeks of therapy
following Week 4 RVR
– Treatment-limiting adverse effects include rash, GI problems
Polymerase inhibitors
 Valopicitabine 200 mg/day plus peginterferon alfa-2a resulted in end of
treatment response in one half of treatment-naive genotype 1 patients
 Poor SVR rates with valopicitabine/peginterferon retreatment
– May be due to high discontinuation rates, lack of ribavirin use
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Conclusions (cont’d)
Polymerase inhibitors (cont’d)
 Viral suppression in ~ one third of treatment-naive patients
receiving HCV-796/peginterferon alfa-2b
Small molecule therapies
 Novel NS4A antagonist ACH-806 displayed strong viral
suppression
– Drug halted due to renal toxicity
 DEBIO-025 effective across genotypes in 14-day treatment trial
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Conclusions (cont’d)
Novel interferons in interferon-naive patients
 Week 12 posttreatment sustained response rates comparable
to standard of care with albinterferon every-4-week dosing
– Significantly better quality of life
 High Week 12 posttreatment sustained response rates with
albinterferon in genotype 2/3 patients
– Best rates in genotype 3 individuals
 36% SVR rate with interferon omega plus ribavirin in
genotype 1 patients
clinicaloptions.com/hep
EASL 2007: Clinical Updates in HCV Treatment
Conclusions (cont’d)
Ribavirin analogues
 Taribavirin associated with significantly lower SVR rates than
ribavirin, except at higher doses
Determining optimal treatment duration
 Extending treatment to Week 72 in slow responders improved
SVR rates vs 48 weeks of treatment
Predictors of SVR
 Week 4 serum ribavirin concentration > 2 mg/L associated with
higher SVR rates
 Poor renal function associated with lower SVR rates in
genotype 1/4 patients
clinicaloptions.com/hep
Go Online for More CCO
Coverage of EASL 2007!
Capsule Summaries of all the key data, plus Expert Analysis panel
discussions exploring the clinical implications
Expert Highlights: download mp3 files and listen to our experts review
the highlights of this conference
Expert Recap (slides and audio) plus
downloadable PowerPoint slides
clinicaloptions.com/barcelona2007