Transcript Document

Jo-Ann Ford, RN, MSN
Associate Director
BC Hepatitis Program
Diamond Centre, VGH
Advances in HCV Treatment Where Are we Going?
Disclosures – J. Ford
• Clinical Trials:
– Hoffmann LaRoche, Merck Canada,
Vertex Inc., Pfizer Canada, Johnson &
Johnson, Gilead Sciences, Human
Genome Sciences, Boehringer Ingelheim
• Advisory Boards:
– Merck Canada, Hoffmann LaRoche,
Gilead Sciences, Vertex Inc.
Introduction
•
Prevalence HCV in Canada: 1-2%
•
BC: Estimated 60,000 – 100,000 chronic
carriers
•
HCV in Canada
– Yesterday: recipients of blood transfusions
– Today: horizontal transmission (IVDU)
HCV: A Global Health Problem
FAR EAST
ASIA
60 M
CANADA 300,000
U.S.A.
4M
SOUTH
AMERICA
10 M
WEST
EUROPE
9M
EAST
MEDITERRANEAN
20M
AFRICA
32 M
SOUTH EAST
ASIA
30 M
AUSTRALIA
0.2 M
170 Million Carriers Worldwide
SOURCE, WHO
3% of World Population
Hepatitis C Disease Progression
5% of chronic
HCV-infected
cirrhotic
individuals per
year
Liver
Cancer
(HCC)
10-20% of
chronic HCVinfected
individuals
Acute
Infection
• 80% of infected
patients progress
to chronic disease
• acute infection
often silent
Chronic
Infection
Cirrhosis
Liver Failure
(Decompensation)
Approx 20% of
patients
decompensate
within 5 years of
developing
cirrhosis
Liver
Transplantation
Death
Chronic HCV is the
leading cause of
liver transplantation
in the US and
Canada
Goals of Treatment
•
Cure HCV infection
•
Suppress disease activity
•
Halt or reverse fibrosis progression
•
Reduce risk of hepatocellular carcinoma
•
Control extrahepatic consequences of
HCV infection
HCV Infection: Extrahepatic
Manifestations
Haematological
•
•
•
•
Mixed cryoglobulinemia
Aplastic anaemia
Thrombocytopenia
Non-Hodgkin’s b-cell lymphoma
Dermatological
• Porphyria cutanea tarda
• Lichen planus
• Cutaneous necrotising
vasculitis
Renal
• Glomerulonephritis
• Nephrotic syndrome
Endocrine
• Anti-thyroid antibodies
• Diabetes mellitus
Ocular
• Corneal ulcer
• Uveitis
Vascular
• Necrotising vasculitis
• Polyarteritis nodosa
• Pulmonary fibrosis
Neuromuscular
• Weakness/myalgia
• Peripheral neuropathy
• Arthritis/arthralgia
Autoimmune
Phenomena
• CREST syndrome
• Granuloma
• Autoantibodies
Salivary
• Sialadenitis
Hadziyannis. J Eur Acad Dermatol Venereol. 1998.
Increasing proportion of liver transplantations
due to HCV
%
% of liver transplant due to Hepatitis C
60
50
UNOS
46
40
30
20
10
0
8
Source: UNOS
6.5
90 91 92 93 94 95 96 97 98 99 00 01 02
Year
Current HCV Therapy: 2010
Genotype 1 in need of better therapies
Sustained Response
80%
60%
38-41%
40%
29%
17%
20%
9%
2%
0%
IFN 24w
IFN 48w
Late 1980’s
HCV hepatitis C virus; IFN interferon
IFN-R 24w
IFN-R 48w
PEG-R
2010
IDEAL
Peginterferon Alfa-2b
or Alfa-2a with Ribavirin for
Treatment of Hepatitis C Infection
McHutchison J et al.
N Engl J Med 2009; 361:580-93.
Study Schema
and Treatment Regimens
Screening
HCV RNAa
24
N = 1019
PEG-IFN alfa-2b 1.5 μg/kg/wk
+ RBV 800-1400 mg/d
× 48 weeks
Follow-up
24 weeks
N = 1016
PEG-IFN alfa-2b 1.0 μg/kg/wk
+ RBV 800-1400 mg/d
× 48 weeks
Follow-up
24 weeks
N = 1035
PEG-IFN alfa-2a 180 μg/wk
+ RBV 1000-1200 mg/d
× 48 weeks
Follow-up
24 weeks
12
24
48
4
12
Stratified by baseline viral load (> or ≤ 600,000 IU/mL) and race (African American)
 Standard response stop criteria applied at weeks 12 (no EVR) and 24 (HCV RNA-positive)

a LLQ
<27 IU/mL (COBAS TaqMan; Roche)
24
Treatment Discontinuation:
Non-Response
• Week 12
– Subjects with TW12 HCV RNA decline < 2 log10 were
discontinued
– Subjects with TW12 HCV RNA decline >2 log10 but not
aviremic were continued on therapy and re-assessed at
treatment week 24
• Week 24
– Subjects who did not achieve aviremia by TW 24 were
discontinued
• Note: similar to current community practice!
Screening, Treatment, and Follow-up
4469 patients screened
3083 met inclusion criteria
and randomised
1386 excluded due to:
Ineligible for protocol, declined, lost to
follow-up, noncompliant, adverse event
13 randomised but not treated
3070 treated:
1019 standard-dose PEG-IFN alfa-2b + RBV
1016 low-dose PEG-IFN alfa-2b + RBV
1035 PEG-IFN alfa-2a + RBV
1416 discontinued treatment:
1654 completed treatment:
830 had treatment failure, 362 had
adverse event, 224 had other reason;
Of these, 383 never entered follow-up
540 standard-dose PEG-IFN alfa-2b + RBV
493 low-dose PEG-IFN alfa-2b + RBV
621 PEG-IFN alfa-2a + RBV
2417 completed follow-up:
812 standard-dose PEG-IFN alfa-2b + RBV
779 low-dose PEG-IFN alfa-2b + RBV
826 PEG-IFN alfa-2a + RBV
SVR Similar Across Treatment Regimens
% of Patients With
Undetectable HCV RNA
80
60
1.5/RBV PEG-IFN alfa-2b vs. PEG-IFN alfa-2a
180/RBV, P=0.57
PEG-IFN alfa-2b 1.5/RBV vs. PEG-IFN alfa-2b
1.0/RBV, P= 0.20
41%
40%
38%
40
20
0
PEG 2b 1.5 /R
(n=1019)
PEG 2b 1.0 /R
(n=1016)
PEG 2a /R
(n=1035)
Advances in Therapy
?
100%
STAT-C
Sustained
virologic
response
rate
Peginterferon
ribavirin
50%
IFN+
ribavirin Peginterferon
(12 months) (12 months)
IFN
(12 months)
IFN
(6 months)
No treatment
1991
1998
2000
HCV Pipeline* by MOA and Stage of Development
Preclinical
STAT-C Combinations
Gilead
NucPolymerase
inhibitors
BI
Phase I
Japan Tobacco
Roche
R0622 (Roche)
Phase II
Nitazoxanide
(Romark)
Others
Vertex
Phase III
PSI938(Pharmasset)
PSI-7977
(Pharmasset)
Biocryst
Filed
Taribavirin
(Valeant)
INX189
(Inhibitex)
ALBUFERON
(HGS/Novartis)
Debio025 and NIM811 cyclophilins
(Novartis)
GL59393 (GSK)
R7128
(Roche/Pharmasset)
Caspase inhib (Gilead)
INF lambda (Zymogen/ NovoNordisk)
Medivir/Tibotec
BMS
filibuvir
(PFE)
Merck
BMS-791325 (nuc or
non-nuc)(BMS)
IDX-184 (Idenix)
AZD7259 NS5A (AZN)
GS9190
(Gilead)
Idenix
ABT333. ABT072
(ABT)
BMS790052 NS5A (BMS)
GSK
Boceprevir
(MRK)
Presidio
TMC-435
(J&J/Tibotec)
Enanta
GS9256
(Gilead)
MK7009
(MRK)
BMS650032 (BMS)
ITMN-191/R7227
(Roche/Intermune)
Vertex
NS5A inhibitors
inhibitors
MK5172
(Merck)
3/2/2010 – selected
compounds only
ANA598
(Anadys)
Telaprevir
(J&J/Vertex)
BMS824393 NS5A (BMS)
ABT450 (ABT)
Protease inhibitors
VX22
(Vertex)
IDX375
(Idenix/NVS)
BI201127 (BI)
BI201335 (BI)
ACH1625 (Achillion)
*Publicly available information via press
release, corporate presentations and
assumptions based on patent filings
Non-Nuc
Polymerase
inhibitors
What will be the
Standard of Care for
Genotype 1 Patients?
CHC, G1, naïve,
n=1097 (incl. 159 AA)
HCV SPRINT-2 – Boceprevir +
PegIntron® + RBV in Naïve G1 –
PegIntron 1.5 µg/kg/wk
plusIII
RBV 600-1400 mg/d
24 wks
Phase
plus placebo (starting at study week 5)
Study
Weeks 0
®
Follow-up
PegIntron® 1.5 µg plus 44 wks Follow-up
PegIntron
RBV 600-1400 mg/d plus PegIntron® plus
24 wks
plus RBV
boceprevir 800 mg tid RBV plus placebo Follow-up
PegIntron
plus RBV
4
PegIntron® 1.5 µg plus RBV 600-1400 mg
plus boceprevir 800 mg tid
8*
28
24 wks
Follow-up
48
72
Randomization (1:1:1, stratified by G1 subtype and BL VL)
* Pts in the 28-wk-arm who are HCV RNA undetectable at week 4 of boceprevir tx (=study
week 8) and all subsequent assays will stop tx at wk 28
Pts who are not undetectable will stop boceprevir at week 28 and will continue with
PegIntron® plus RBV alone for an additional 20 weeks
Poordad et al, AASLD 2010, oral (LB-4), Bronowicki et al, AASLD 2010, poster (LB-15)
SPRINT-2 – SVR (ITT)
*
*
* p<0.0001
Per protocol, if a pt did not have a 24-week post-tx assessment, the patient’s 12-week posttx assessment was utilized
Press release, August 4, 2010
SPRINT-2: SVR Rates in Patients Who
Qualified For 28 Weeks of Therapy
 44% of patients qualified for 28 weeks of therapy (assessment at
Week 4 of BOC, ie Week 8 of therapy) in response-guided arm
100
97
87
SVR (%)
80
60
40
20
0
n/N = 143/147
Non-blacks
13/15
Blacks
SPRINT-2: SVR and Relapse Rates (ITT)
4-wk PR + response-guided BOC/PR
4-wk PR + 44 weeks BOC/PR
Nonblack Patients
100
48-wk PR
Black Patients
100
P < .0001
80
67
60
40
40
23
20
9
0
P = .044
68
Patients (%)
Patients (%)
80
n =211 213 125
SVR
60
53
42
40
23
20
12
8
21 18 37
Relapse
Poordad F, et al. AASLD 2010. Abstract LB-4
P = .004
0
22
29
SVR
12
3
17
14
6
2
Relapse
SPRINT-2 –
Discontinuation due to Adverse Events
Poordad et al, AASLD 2010, oral (LB-4)
Boceprevir: Adverse Events
• Anemia and dysgeusia reported more frequently
in BOC arms vs control in SPRINT-2
Outcome
4-Wk PR +
4-Wk PR + 44Response-Guided
Wk BOC/PR
BOC/PR
(n = 366)
(n = 368)
48-Wk PR
(n = 363)
Adverse event, %
• Anemia[1]
49
49
29
• EPO use
41
46
21
• Dysgeusia[2]
37
43
18
• Anemia discont.
2
2
1
1. Poordad F, et al. AASLD 2010. Abstract LB-4.
Telaprevir in Combination with
Peginterferon Alfa-2a and Ribavirin in
Genotype 1 HCV Treatment-Naïve patients:
Final Results of Phase 3 ADVANCE Study
Ira M. Jacobson, John G. McHutchison, Geoffrey M. Dusheiko,
Adrian M. Di Bisceglie, Rajender Reddy, Natalie H. Bzowej,
Patrick Marcellin, Andrew J. Muir, Leif Bengtsson, Ann Marie
Dunne, Nathalie Adda, Shelley George, Robert S. Kauffman
and Stefan Zeuzem
ADVANCE: Study Design
Randomized, Double-Blind, Placebo-Controlled for TVR
eRVR +
Follow-up
T12PR
TVR + PR
T8PR
Follow-up
SVR
Pbo
+
PR
PR
eRVR +
Follow-up
Follow-up
.
SVR
Follow-up
PR
SVR
eRVR-
PR
Follow-up
.
SVR
PR48
(control)
Weeks
SVR
PR
eRVR-
TVR
+
PR
72 weeks
Pbo + PR
0
8
Follow-up
PR
12
24
36
48
72
eRVR = HCV RNA undetectable at week 4 and week 12, Response-guided therapy
(T) TVR = telaprevir 750 mg q8h; Pbo = Placebo; (P) Peg-IFN = pegylated interferon alfa-2a (40 kD) 180 µg/wk;
(R) RBV = ribavirin 1,000 or 1,200 mg/day
Presented at AASLD – November 2, 2010
Roche Taqman® v2 LLOQ of 25 IU/mL
Demographics and Baseline
Characteristics
T12PR
N = 363
T8PR
N = 364
PR
N = 361
Gender, n (%)
Male
214 (59)
211 (58)
211 (58)
Race†, n(%)
Caucasian
Black/African American
325 (90)
26 (7)
315 (87)
40 (11)
318 (88)
28 (8)
Ethnicity, n (%)
Hispanic/Latino
35 (10)
44 (12)
38 (11)
Age, median years (range)
49 (19-69)
49 (19-68)
49 (18-69)
BMI, median kg/m2 (range)
26 (18-47)
26 (17-46)
26 (17-48)
HCV RNA ≥ 800,000 IU/mL*, n (%)
281 (77)
279 (77)
279 (77)
HCV Genotype Subtype**, n (%)
1a
1b
1, unknown
213 (59)
149 (41)
1 (<1)
210 (58)
151 (41)
3 (1)
208 (58)
151 (42)
2 (1)
Stage of fibrosis or cirrhosis, n (%)
Bridging Fibrosis
Cirrhosis
52 (14)
21 (6)
59 (16)
26 (7)
52 (14)
21 (6)
†Race
and ethnicity were self-reported
**5’NC InnoLipa assay
*Roche Taqman® v2 LLOQ of 25 IU/mL
Presented at AASLD – November 2, 2010
SVR rates in Telaprevir-Treated Patients
Compared to Peginterferon/Ribavirin Alone
T12PR
PR
P<0.0001
100
Percent of patients with SVR
T8PR
90
P<0.0001
75
80
69
70
60
44
50
40
30
20
10
0
n/N =
271/363
250/364
158/361
SVR
Presented at AASLD – November 2, 2010
Undetectable HCV RNA at Week 4 (RVR)
and Weeks 4 and 12 (eRVR)
T12PR
100
Percent of patients with
HCV RNA undetectable
90
68
PR
Patients eligible to
receive 24 weeks
of total treatment
80
70
T8PR
66
58
60
57
50
40
30
20
9
10
8
0
n/N = 246/363 242/364
34/361
Week 4 (RVR)
212/363 207/364 29/361
Weeks 4 and 12 (eRVR)
Presented at AASLD – November 2, 2010
SVR Rates by eRVR Status
97
Percent of patients with SVR
100
90
89
T12PR
T8PR
PR
83
80
70
60
54
50
50
39
40
30
20
10
0
n/N = 189/212 171/207
24-week regimen
eRVR+
28/29
82/151
79/157
130/332
48-week regimen
eRVRPresented at AASLD – November 2, 2010
ADVANCE AEs leading to DC and most common AEs
% Pts. with
T12PR
T8PR
PR
Any AE
99
99
98
Fatigue
57
58
57
Pruritus
50
45
36
Headache
41
43
39
Nausea
43
40
31
Rash
37
35
24
Anemia
37
39
19
Insomnia
32
32
31
Diarrhea
28
32
22
Flu-like
symptoms
28
29
28
Pyrexia
26
30
24
Events occurring >10% in any TVR group vs. Placebo are shaded.
ADVANCE – Discontinuation of
Treatment due to Rash and Anemia
Jacobson et al, AASLD 2010, oral (211)
What will be the
Approach for
PegIFN and Ribavirin Failures?
Virologic Response Patterns
with Peg-IFN/RBV: Treatment Failure
HCV RNA level
Partial response
Non-response
Null response
Relapse
2 log10 drop
Detection limit
Treatment
0
4
8
12 16 20 24 28 32 36 40
44 48 52 56 60 64 68 72
Weeks
Adapted from Shiffman ML. Curr Gastroenterol Rep 2006;8:46–52
34
HCV RESPOND-2 Final Results
High Sustained Virologic Response Among Genotype 1
Previous Non-Responders and Relapsers to
Peginterferon/Ribavirin when Re-Treated with Boceprevir
Plus PEGINTRON (Peginterferon alfa-2b)/Ribavirin
Bruce R. Bacon, Stuart C. Gordon, Eric Lawitz, Patrick
Marcellin, John M. Vierling, Stefan Zeuzem, Fred Poordad,
Navdeep Boparai, Margaret Burroughs, Clifford A. Brass,
Janice K. Albrecht, and Rafael Esteban
For the RESPOND-2 Investigators
RESPOND-2: Study Objectives
•
Compare safety/efficacy of two treatment
strategies with boceprevir added to
peginterferon/ribavirin (PR) versus PR alone
in genotype 1 patients who failed treatment
with PR
•
Evaluate safety/efficacy independently in two
patient populations, history PR non-responders
(decrease of HCV-RNA ≥2-log by week 12 of
prior therapy but with detectable HCV-RNA
throughout the course of therapy) and
relapsers
•
Explore response-guided therapy (RGT) vs. 44
weeks of therapy with boceprevir regimen
(BOC/PR48)
Study Arms and Dosing Regimen
Control
48 P/R
N = 80
Week
4
PR
lead-in
Week 36
PR + Placebo
Follow-up
Follow-up
PR + Boceprevir
TW 8 HCV-RNA
Detectable/
TW 12 Undetectable
PR +
placebo
BOC/
PR48
N = 161
PR
lead-in
Week 72
TW 8 HCV-RNA Undetectable
Week 12
futility
BOC
PR
RGT
lead-in
N = 162
Week 48
PR + Boceprevir
Follow-up
Follow-up
HCV-RNA measured by the Cobas TaqMan assay (Roche). Patients with detectable HCV-RNA (LLD=9.3
IU/mL) at week 12 were considered treatment failures.
Peginterferon (P) administered subcutaneously at 1.5 μg/kg once weekly, plus Ribavirin (R)
using weight based dosing of 600-1400 mg/day in a divided daily dose
Boceprevir dose of 800 mg thrice daily
RESPOND-2: SVR Rates According to
Treatment Arm and Prior Response
100
P < .0001 vs
control
(both arms)
4-wk PR + response-guided
BOC + PR (n = 162)
80
69
SVR (%)[1]
67
60
4-wk PR + 44-wk
BOC + PR (n = 161)
75
48-wk PR (n = 80)
59*
52
40
40
29
20
21
7
0
Overall
Prior
Nonresponders
*46% of patients in
response-guided arm
eligible for shorter
duration of therapy,
with 86% SVR rate.[2]
Prior
Relapsers
1. Bacon BR, et al. AASLD 2010. Abstract 216. These data are available in unpresented abstract format only and will be
presented in full during the AASLD meeting. We encourage you to review the presented data before making conclusions.
2. These data are available in press release format only, have not been peer reviewed, may be incomplete, and we await
presentation or publication in a peer-reviewed format before conclusions should be made from these data.
Telaprevir-based Therapy in Genotype 1
Hepatitis C Virus-infected Patients with
Prior Null Response, Partial Response or
Relapse to Peginterferon/Ribavirin:
REALIZE Trial Final Results
Graham R Foster,1 Stefan Zeuzem,2 Pietro Andreone,3 Stanislas
Pol,4 Eric Lawitz,5 Moises Diago,6 Stuart Roberts,7 Roberto
Focaccia,8 Zobair Younossi,9 Andrzej Horban,10 Rolf Van
Heeswijk,11 Sandra De Meyer,11 Don Luo,12 Gaston Picchio,12 Maria
Beumont11
1Queen
Mary University of London, Institute of Cell and Molecular Science, London, UK; 2Johann
Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 3Università di Bologna,
Bologna, Italy; 4Université Paris Descartes, INSERM Unité 567, and Assistance Publique–Hôpitaux de
Paris, Cochin Hospital Paris, France; 5Alamo Medical Research, San Antonio, TX, USA; 6Hospital
General de Valencia, Valencia, Spain; 7Department of Gastroenterology, Alfred Hospital, Melbourne,
Australia; 8Emilio Ribas Infectious Diseases Institute, São Paulo, Brazil; 9Center for Liver Disease,
Inova Fairfax Hospital, Falls Church, VA,USA; 10Medical University of Warsaw, Wolska, Warsaw,
Poland; 11Tibotec BVBA, Beerse, Belgium; 12Tibotec Inc., Titusville, NJ, USA
Presented at APASL, 18 February 2011
44
REALIZE: Study Objectives
•
International, randomized, double-blind,
multicentre, placebo-controlled Phase III trial
•
Primary objective:
•
– To evaluate superior efficacy (proportion of patients
achieving an SVR) of TVR-based therapy compared
with standard treatment in patients within the prior
relapser and prior-non-responder (partials/nulls)
group
Key secondary objectives:
– Evaluation of effect of Peg-OFN/RBV lead-in on
efficacy of TVR-based treatment
– Assessment of safety and tolerability of TVR-based
treatment
REALIZE Study Design (N=662)*
T12/PR48
TVR + Peg-IFN +
RBV
n=266
T12(DS)/
PR48
n=264
Pbo +
Peg-IFN
+ RBV
Pbo +
Peg-IFN
+ RBV
TVR+
Peg-IFN + RBV
Peg-IFN + RBV
Follow-up
Peg-IFN + RBV
Follow-up
Peg-IFN + RBV
Follow-up
Pbo/PR48
Pbo +
Peg-IFN + RBV
(control)
n=132
0
4
8
12
16
48
Weeks
72
SVR assessment
*Randomization stratified by viral load and prior response; stopping rules applied for TVR (Weeks 4, 6, and 8) and
Peg-IFN/RBV (Weeks 12, 24, and 36)
Peg-IFN = 180μg/week; RBV = 1000–1200mg/day; TVR = 750mg every 8 hours
ClinicalTrials.gov identifier: NCT00703118
Pbo = placebo; DS = delayed start
Presented at APASL, 18 February 2011
REALIZE: Baseline Characteristics
T12/PR48
(n=266)
T12(DS)/PR48
(n=264)
Pbo/PR48
(n=132)
Male, n (%)
183 (69)
189 (72)
88 (67)
Caucasian race, n (%)
246 (92)
252 (95)
117 (89)
11 (4)
8 (3)
11 (8)
51 (23–69)
51 (24–70)
50 (21–69)
238 (89)
234 (89)
114 (86)
HCV genotype, n (%)‡
1a
1b
136/262 (52)
126/262 (48)
149/262 (57)
113/262 (43)
67/128 (52)
61/128 (48)
Prior response, n (%)
Null responder
Partial responder
Relapser
72 (27)
49 (18)
145 (55)
75 (28)
48 (18)
141 (53)
37 (28)
27 (20)
68 (52)
Bridging fibrosis, n (%)§
60 (23)
58 (22)
29 (22)
Cirrhosis, n (%)§
72 (27)
67 (25)
30 (23)
Characteristic
Black race, n (%)
Years of age, median (range)
HCV RNA ≥800,000 IU/mL, n (%)*
*Determined using the COBAS TaqMan HCV assay version 2.0; ‡Determined by NS3 sequencing; §Defined by local pathologists
Presented at APASL, 18 February 2011 47
REALIZE: SVR in Prior Relapsers, Partial
Responders and Null Responders
Prior
relapsers
*
Prior null
responders
*
*
SVR (%)
n/N=
Prior partial
responders
*
*
*
T12/
PR48
T12(DS)/
PR48
Pbo/
PR48
T12/
PR48
T12(DS)/
PR48
Pbo/
PR48
T12/
PR48
T12(DS)/
PR48
Pbo/
PR48
121/145
124/141
16/68
29/49
26/48
4/27
21/72
25/75
2/37
*p<0.001 vs Pbo/PR48
Presented at APASL, 18 February 2011 48
AEs Leading to Study Drug Discontinuations
T12/PR48
(n=266)
T12(DS)/PR
48 (n=264)
Pbo/PR48
(n=132)
Discontinuation of All Study Drugs during TVR Treatment Phase, n (%)
Any AE
17 (6)
11 (4)
4 (3)
Rash events
2 (1)
2 (1)
0
Anemia events
2 (1)
2 (1)
0
0
1 (<1)
0
Pruritus
Discontinuation of TVR during TVR Treatment Phase, n (%)
Any AE
Rash events
Anemia events
Pruritus
39 (15)
29 (11)
4 (3)
12 (5)
10 (4)
0
6 (2)
9 (3)
0
1 (<1)
3 (1)
0
AE = adverse event
Presented at APASL, 18 February 2011
49
REALIZE: Conclusions
•
TVR/Peg-IFN/RBV was superior to PegIFN/RBV in treatment experienced
populations including null responders, partial
responders and relapsers
•
A lead-in strategy using TVR-based regimen
did not improve SVR rates or reduce ontreatment virologic failure and relapse rates
•
Safety data were comparable to previous TVR
studies. Adverse events leading to permanent
discontinuation (anemia and rash) were more
frequent in the pooled telaprevir group then in
the control group
Presented at APASL 18 Feb 2011
CONCLUSIONS
• The future is very bright, with greater
opportunity for CURE
• Boceprevir/Telaprevir associated with
higher SVR rates
• Shorter duration (response-guided therapy)
• Protease inhibitors & PegIFN/Ribavirin
expected to be the next standard of care for
HCV Genotype 1
CONCLUSIONS
• The future is very bright for our Treatment
Failure patients
• Boceprevir/Telaprevir will set a new
standard for our treatment-experienced