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Hepatitisweb study
Hepatitisweb study
Telaprevir in Treatment Naïve GT-1ADVANCE (Study 108)
Phase 3
Treatment Naïve
Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE: Study Design
Drug DosingTelaprevir = 750 mg every 8 hoursPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/day for wt < 75 kg; 1200 mg/day for wt > 75 kg
ADVANCE: Study Features
N = 1,088 enrolled Randomized, double-blind, placebo-controlled, Phase 3 trial Genotype 1 HCV and treatment naïve 77% with HCV RNA ≥ 800,000 IU/ml Randomized to one of 3 arms RVR = HCV RNA undetectable at week 4 eRVR = HCV RNA undetectable at weeks 4 & 12 Erythroid stimulating agents not allowed Telaprevir-treated patients without eRVR received PR up to week 48
Hepatitisweb study
Telaprevir+
PEG + RBV
eRVR: PEG + RBV
No eRVR: PEG + RBV
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Treatment Regimens
8 24 48Week 0
Telaprevir+
PEG + RBV
Placebo+
PEG + RBVPEG + RBV
12
T8
PR 24 or 48
T12
PR 24 or 48
PR48
N =364
N =363
N =361
PEG +
RBV
eRVR: PEG + RBV
No eRVR: PEG + RBV
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results
ADVANCE: SVR24 by Regimen
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
T8/PR24 or 48 T12/PR24 or 48 PR 480
20
40
60
80
100
6975
44
Pat
ien
ts w
ith
SV
R (
%)
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
250/364 271/363 158/361
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: RVR and eRVR Rates
ADVANCE: Patients with RVR and eRVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
RVR (week 4) eRVR (week 12)0
20
40
60
80
100
66
57
68
58
9 8
T8/PR24 or 48T12/PR24 or 48PR48
Pat
ien
ts (
%)
T = Telaprevir; PR = Peginterferon + Ribavirin; RVR = rapid virologic response; eRVR = extended rapid virologic response
242/364 246/363 34/361 207/364 212/363 29/361
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results According to eRVR
ADVANCE: SVR24 by eRVR Status
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
With eRVR Without eRVR0
20
40
60
80
100
83
50
89
54
97
39
T8/PR24 or 48T12/PR24 or 48PR48
Pat
ien
ts w
ith
SV
R (
%)
T = Telaprevir; PR= Peginterferon + Ribavirin; SVR = Sustained Virologic ResponseeRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)
171/207 189/212 28/29 79/157 82/151 130/342
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results According to eRVR
ADVANCE: SVR24 by eRVR Status
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
T8/PR24 or 48 T12/PR24 or 48 PR 480
20
40
60
80
100
8389
97
5054
39
With eRVR Without eRVR
Pat
ien
ts w
ith
SV
R (
%)
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin; eRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)
171/207 189/212 28/2979/157 82/151 130/342
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results According to Race
ADVANCE: SVR24 by Race
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
White Black Hispanic0
20
40
60
80
100
70
5866
75
62
74
46
25
39
T8/PR 24 or 48 T12/PR24 or 48 PR48
Pat
ien
ts w
ith
SV
R (
%)
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
221/315 147/318 16/26244/325 7/28 26/35 15/3829/4423/40
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results by Baseline HCV RNA
ADVANCE: SVR24 by Baseline HCV RNA Level
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
< 800,000 IU/ml ≥800,000 IU/ml 0
20
40
60
80
100
79
66
7874
70
36
T8/PR 24 or 48 T12/PR24 or 48 PR48
Baseline HCV RNA Level
Pat
ien
ts w
ith
SV
R (
%)
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
184/279 207/28164/82 57/8267/85 101/279
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Results by Fibrosis Stage
ADVANCE: SVR24 by Fibrosis Stage
Source: Jacobson IM, et. al. Hepatology. 2010;52 (Supplement 1):427A. Abstract 211.
No or Minimal Fi-brosis
Portal Fibrosis Bridging Fibrosis Cirrhosis0
20
40
60
80
100
79
69
58
42
8175
62 62
46 48
33 33
T8/PR24 or 48 T12/PR24 or 48 PR48
Pat
ien
ts w
ith
SV
R (
%)
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
101/128 109/134 67/147 104/151 117/156 67/141 17/52 7/2132/52 13/2134/59 11/26
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Adverse Effects
ADVANCE: Percentage of Patients with Anemia
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Hb < 10 g/dL Hb < 8.5 g/dL0
10
20
30
40
50
60
40
9
36
914
2
T8/PR24 or 48
T12/PR24 or 48
PR48
Hemoglobin (Hb) Nadir Through Week 12
Pat
ien
ts (
%)
T = Telaprevir; PR = Peginterferon + Ribavirin
146/364 33/364 33/363131/363 7/36151/361
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Adverse Effects
ADVANCE: Percentage of Patients with Rash
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Rash Severe (Grade 3) Rash0
10
20
30
40
50
60
35
4
37
6
24
1
T8/PR24 or 48
T12/PR24 or 48
PR48
Pat
ien
ts (
%)
T = Telaprevir; PR = Peginterferon + Ribavirin
15/36422/363
4/361129/364 133/363 88/361
Hepatitisweb study
Telaprevir for Treatment-Naïve HCV Genotype 1SVR Rates by IL28B rs12979860 Genotype
ADVANCE: SVR24 by rs12979860 Genotype
Source: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.
PR48 T12/PR24 or 480
20
40
60
80
100
23
73
25
7164
90
T/T C/T C/C
Treatment Regimen
Pat
ien
ts w
ith
SV
R (
%)
PR48 = Peginteron/Ribavirin x 48 weeks PR/T12 = Peginteron/Ribavirin + Telaprevir x 12 weeks
45/5035/556/26 16/2220/80 48/68
Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Telaprevir for Treatment-Naïve HCV Genotype 1ADVANCE Study: Conclusions
Conclusions: “Telaprevir with peginterferon–ribavirin, as compared with
peginterferon–ribavirin alone, was associated with significantly improved
rates of sustained virologic response in patients with HCV genotype 1
infection who had not received previous treatment, with only 24 weeks of
therapy administered in the majority of patients.”