Asian-Pacific Consensus Statement on the Management of
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Transcript Asian-Pacific Consensus Statement on the Management of
Entering an era of individualised
treatment for chronic hepatitis C
Antiviral therapy in 2014 & beyond
Ed Gane
NZ Liver Transplant Unit
Auckland City Hospital
Factors associated with Treatment Response
VIRAL FACTORS
HCV Genotype
Viraemia level
HIV infection
HOST FACTORS
IL28b Genotype
African Race
Older age
Obesity/DM
DISEASE FACTORS
cirrhosis
TREATMENT FACTORS
Resistance
Adherence
SVR24 rates with PEG/RBV by HCV genotype
Patients with GT2/3 are
Data from the real-world PROPHESYS cohort study
easier to treat with
Treatment-naive patients treated with Pegasys or PegIntron plus RBV
SVR24 (%)
PegIFN/RBV
n
N
1891
4119
732
913
763
1063
130
282
HCV genotype
* Patients with sufficient follow-up data.
Marcellin P, et al. Hepatology 2012; 56:2039–2050.
SVR24 rates with PEG/RBV by Fibrosis Stage
SVR24 (%)
Patients without
cirrhosis are easier to
treat with PegIFN/RBV
n
N
37
63
143
261
257
631
188
495
26
142
METAVIR fibrosis stage
Ferenci P, et al. Hepatol Int 2014; 8:83–93.
SVR24 rates with PEG/RBV by IL28B genotype
SVR24 (%)
Patients with an IL28B
CC genotype are
easier to treat with
PegIFN/RBV
n
N
102
129
84
192
21
51
Proportion of patients
with IL28B genotype
Stättermayer AF, et al. Clin Gastroenterol Hepatol 2011; 9:344–350.
SVR24 rates with PEG/RBV by IL28B genotype
CC allele frequency
Maori,
Pacific Islander and
stratified by race2
Asian patients are easier
to treat with PegIFN/RBV
Rate of SVR and CC allele frequency
in diverse ethnic groups1
EuropeanAmericans
Hispanics
African-Americans
CC frequency (%)
SVR24 (%)
Maori/
Pacific Is
East Asians
rs12979860 C allele frequency
1. Ge D, et al. Nature 2009; 461:798–801;
2. Jiménez-Sousa MA, et al. BMC Medicine 2013; 11:6 (supplementary information).
Targets in the HCV Life Cycle for
Direct Acting Antiviral Agents
Receptor binding
and endocytosis
Transport
and release
Fusion and
uncoating
Virion
assembly
ER lumen
(+) RNA
LD
Translation and
polyprotein
processing
LD
NS5A inhibitors
LD
Membranous
web
ER lumen
NS3 Protease Inhibitors
RNA replication
Non-Nuc NS5B inhibitors
NUC NS5B inhibitors
Protease Inhibitors in Clinical Development
Target
NS3/4a Serine
Protease
Agent
Company
Phase
Boceprevir
Telaprevir
Simeprevir
Merck
Vertex
Tibotec
Approved
Approved
Approved
Vaniprevir
Faldaprevir
Merk
Boehringer
Phase III
Phase III
Asunaprevir
BMS
Phase II
ABT450
Abbott
Phase III
Danoprevir
Roche
Phase III
MK5172
Merck
Phase II
SCH900518
GS 9256
GS 9451
VX-985
ACH1625
IDX-320
ACH1284
BMS-791325
VX-500
PHX1766
Merck
Gilead
Gilead
Vertex
Achillon
Idenix
Achillon
BMS
Vertex
Pfizer
Phase II
Phase II
Phase II
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Addition of BOC or TVR to PEG/RBV in HCV GT-1
Higher SVR rates in Treatment Naïve Patients
∆ 31%
SVR24 (%)
∆ 28%
n
N
242
366
137
363
1
PI = protease inhibitor.
271
363
158
361
2
1. Poordad F, et al. N Engl J Med 2011; 364:1195‒1206;
2. Jacobson IM, et al. N Engl J Med 2011; 364:2405‒2416.
Addition of BOC or TVR to PEG/RBV in HCV GT-1
SVR depends on prior response to PEG/RBV
100
70–86
63–79
SVR (%)
80
Treatment-naive/relapser
patients are easier to treat
with PI/PegIFN/RBV
40–59
60
32–38
40
20
0
Prior
relapse1,2
Naive
patients1,2
Prior partial
response1–3
Prior null
response1,2
1. BOC prescribing information, revised February 2014;
2. TVR prescribing information, revised October 2013;
3. Bacon BR, et al. N Engl J Med 2011; 364:1207–1217.
Addition of BOC or TVR to PEG/RBV in HCV GT-1
Higher SVR rates in HCV Subtype 1b
TVR2
HCV GT1b patients
are
easier to treat with
PI/PegIFN/RBV
BOC1
∆ 8%
SVR24 (%)
SVR24 (%)
∆ 7%
n 242
N 366
137
363
P/R = peginterferon alfa/ribavirin.
118
187
62
177
93
133
51
126
n 271
N 363
158
361
152
213
85
208
118
149
73
151
1. Poordad F, et al. N Engl J Med 2011; 364:1195‒1206 (supplementary information);
2. Jacobson IM, et al. N Engl J Med 2011; 364:2405‒2416.
1st Gen Protease inhibitors have reduced
efficacy in HCV subtype 1a
V36M Protease resistance
ATC
ATG
(V36) (V36M)
2 steps
GTG
ATG
GTC
(V36)
(V36) (V36M)
Subtype 1a
1 step
GTC
ATC
GTC
(V36)
(V36) (V36)
Subtype 1b
www.hivforum.org
Simeprevir (OLYSIOTM / TMC435)
NS3 protease
SMV
•
Truncated peptide form
of the 4A co-factor
•
•
•
•
once-daily, oral NS3/4A macrocyclic
protease inhibitor
Multigenotypic: antiviral activity in patients
infected with GT 1, 2, 4, 5, and 61–4
Safe and well tolerated in approximately
3,800 patients – no rash or anemia
inhibits OATP1B1/MRP2 transporters
mild unconjugated bilirubin
investigated as triple therapy with
PEG/RBV and in IFN-free combinations
1. Reesink HW et al. Gastroenterology 2010;138:913-21; 2. Moreno C et al. J Hepatol. 2012;56:1247-53;
3. Zeuzem S et al. Gastroenterology 2014;146:430-41; 4. Fried MW et al. Hepatology 2013:58:1918-25;
5. Jacobson I et al. EASL 2013; 6. Manns M et al. EASL 2013; 7. Forns X et al. Gastroenterology 2014; in press
Simeprevir plus PEG/RBV in HCV GT-1
Treatment Naïve: QUEST-1 (n=394)
: HCV RNA <LLQ at Wk 4 and <LOD at Wk 12
n=260
n=133
85% met RGTstopped at 24 wks
91%
100%
80%
% SVR12
75%
50%
50%
21%
25%
0%
48 wk PR
TMC12PR24
Met RGT
No RGT
Jacobson I, et al. EASL April 2013
Simeprevir plus PEG/RBV in HCV GT-1
Treatment Naïve: Baseline Predictors
100
SVR12 (%)
80
95
80
84
SVR reduced by
• Baseline cirrhosis
• IL28-B non-CC
85
• Q80K in Subtype 1a
75
75
68
58
60
Q80K Prevalence
Nil in Subtype 1b
<10% European GT-1a
>40% of US GT-1a
what about ANZ?
40
20
0
All
F0–2 F3–4
CC Non-CC
METAVIR
IL28B GT
GT1a GT1a GT1b
+Q80K
HCV GT1 subtype
Simeprevir prescribing information, November 2013.
Triple Therapy cannot meet the unmet
medical need in patients with HCV?
1. Poor tolerability
•
•
•
Still requires Pegylated Interferon and ribavirin
Added toxicities of the PIs
Poor safety in advanced liver disease
2. Complex dosing regimen
•
•
Up to 18 tablets - 8 hourly, with high-fat meal
Frequent on-treatment monitoring required
– Response-Guided Therapy and Futility Rules
3. Limited Efficacy
•
•
•
•
Null responders
Subtype 1a
Q80K at baseline
HCV genotypes other than 1
HCV Non-1 GT: Almost 50% Global HCV Population
Denmark
3a
United Kingdom
45
1a
2b
Russia
4 1a
1b
3a
China
1b
1a
2b
2a
France
4 5
3
United States
3a 4 6
2
1b
1a
1a
2
1b
India
3b 4 1a 1b
2
3
1b
2
Vietnam
1b
Korea
3
1
Egypt
13
6
3a
Thailand
6
Brazil
3
2
4
3
1
1b
2a
2
3
1
Genotype 2
Australia
4 6
Genotype 3
Genotype 4
3
1
Genotype 6
Sources: MSD data on file. International Conquer C Coalition (I-C3), Kromite.
Sievert W, et al. Liver Int 2011;31(Suppl 2):61–80
2
Inhibitors of the Polymerase Complex
Target
Agent
Phase
NS5b Non-nucleoside
analogue (NNA)
Deleobuvir
ABT-333
GS-9669
Setrobovir
Filibuvir
Tegobuvir
ABT-072
JTK-003
TMC647055
BMS-824393
VX-222
MK-3281
MK-8876
HCV-796
IDX375
VX759
PF4878691
Phase III
Phase III
Phase II
Phase II
Phase II
Phase II
Phase II
Phase II
Phase II
Phase II
Phase II
Phase II
Phase I
Phase I
Phase I
Phase II
Phase I
Target
Agent
Phase
Cyclophyllin B
inhibitors
Alisporivir
NIM811
Phase III
Phase I
SYC-635
Phase I
Target
NS5b
Nucleoside
Analogue (NA)
Agent
Sofosbuvir
Mericitabine
VX-135
INX-189/BMS-986094
PSI-938
NM283
IDX184
GS-6620
IDX20963
ACH-3422
Phase
Approved
Phase III
Phase II
Phase II
Phase II
Phase II
Phase I
Phase I
Phase I
Phase I
Target
NS5a Nonnucleoside
analogue
Agent
Daclatasvir
Ledipasvir
ABT-267
GS-5816
MK-8742
Phase
Phase III
Phase III
Phase III
Phase II
Phase II
ACH-3102
GSK-2336805
BMS82439
PPI-668
IDX719
Phase II
Phase II
Phase II
Phase II
Phase II
IFN-free DAA therapy in
HCV GT-2 or 3
Sofosbuvir+RBV without PEG in HCV GT2/3
Phase 3 Programme
Week
0
12
16
24
36
FISSION
PEG/RBV (SOC) (n=243)
SVR12
SOF+RBV (n=256)
SVR12
Lawitz E, et al. N Engl J Med 2013;368:1878-87.
FUSION
SOF+RBV (n=98)
SVR12
Jacobson IM, et al. N Engl J Med 2013;368:1867-77.
VALENCE
SOF+RBV (n=207)
SVR12
Zeuzem S, et al. N Engl J Med 2014; online 4 May DOI: 10.1056
Sofosbuvir+RBV without PEG in HCV GT2/3
Phase 3 Programme
Cure (%)
(a) HCV Genotype 2
(b) HCV Genotype 3
Dec 2014: FDA recommends
12 weeks SOF+RBV for GT-2
24 weeks SOF+RBV for GT-3
PEG/RBV SOF/RBV SOF/RBV SOF/RBV
24 wks
12 wks
16wks
24 wks
Lawitz E, et al. N Engl J Med 2013;368:1878-87.
Jacobson IM, et al. N Engl J Med 2013;368:1867-77.
PEG/RBV SOF/RBV SOF/RBV SOF/RBV
24 wks
12 wks
16wks 24 wks
Zeuzem S, et al. N Engl J Med 2014; online 4 May DOI: 10.1056
What about IFN-free DAA
therapy in HCV GT-1?
Sofosbuvir+RBV without PEG in HCV GT1
Phase 2 studies (ELECTRON, QUANTUM, SPARE)
SVR (%)
Adding a second antiviral with
adifferent mechanism of action should
enhance efficacy of SOF+RBV in GT 1
14/25 21/25
14/25
13/25 26/35
Treatment-Naïve
12 weeks1
1Gane
26/35
1/10
13/25
Treatment-Naïve Treatment-Naïve
24 weeks2
24 weeks3
E, et al. NEJM 2013;368:34–44; 2Osinusi A, et al. JAMA. 2013;310:804-11; 3Lalezari J, et al. J Hepatol 2013;58:S236
26
Sofosbuvir plus PEG/RBV in HCV GT-1
NEUTRINO: Study Design
Week 0
12
24
SOF + Peg-IFN + RBV, n=327
SVR12
Open label
– SOF 400 mg QD + Peg-IFN-alfa-2a 180 µg/week +
RBV 1000‒1200 mg/day for 12 weeks (no RGT)
Treatment-naïve, genotype 1, 4, 5, and 6
– 20% cirrhosis, platelets >90
– No upper limit to age or BMI
– Opiate replacement therapy permitted
Lawitz E, et al. N Engl J Med 2013;368:1878-87.
27
Sofosbuvir plus PEG/RBV in HCV GT-1
Efficacy according to baseline factors:
(i) HCV Genotype
100
90
96
(ii) Cirrhosis
100
100
90
SVR12 (%)
80
80
80
60
60
40
40
20
20
262/
292
27/28
7/7
GT 1
GT 4
GT 5,6
0
253/273
43/54
0
No cirrhosis
Cirrhosis
Error bars represent 95% confidence intervals
Lawitz E, et al. N Engl J Med 2013;368:1878-87.
28
Sofosbuvir plus PEG/RBV in HCV GT-1
Safety compared to PEG/RBV and SOF/RBV
Study
Depression
Severe Adverse
Event
Treatment
Discontinuation
PEG/RBV
24 wks
(n=249)
12%
13%
11%
SOF/PEG/RBV
12 wks
(n=327)
5%
2%
1%
SOF/RBV
12 wks
(n=530)
<1%
4%
<1%
Lawitz E, et al. N Engl J Med 2013;368:1878-87.
29
Combining NS5A inhibitor Ledipasvir with a
NUC NS5B polymerase inhibitor Sofosbuvir
Ledipasvir
LDV
NS5A
inhibitor
– Picomolar potency against
HCV GT 1a and 1b1
– Once-daily, oral, 90-mg
Sofosbuvir
– Potent antiviral activity against HCV GT 1–6
– High barrier to resistance
– Once-daily, oral, 400-mg tablet approved for
use with other agents to treat HCV
SOF
Nucleotide
polymerase
inhibitor
Ledipasvir/Sofosbuvir FDC2
– Once daily, fixed-dose (90/400 mg)
combination tablet
– No food effect
– >2000 patients treated
1. Lawitz E, et al. EASL 2011, poster 1219.
SOF
Nucleotide
polymerase
inhibitor
LDV
NS5A
inhibitor
Combining 2 or more DAAs will shorten duration
and increase efficacy: Gilead Dual DAA regimen
Phase III studies in non-transplant HCV (ION-1,2,3)
– Ledipasvir + Sofosbuvir for 8, 12, or 24 weeks
(a) Treatment-naïve
SOF/LDV
100
94
93
95
98
97
SOF/LDV+RBV
98
99
SVR12 (%)
80
60
40
20
0
8 weeks
12 weeks
Afdhal N, et al NEJM 2014;370:1889-98.
Kowdley K, et al. NEJM 2014; 370:1879-88.
24 weeks
Combining 2 or more DAAs will shorten duration
and increase efficacy: Gilead Dual DAA regimen
Phase III studies in non-transplant HCV (ION-1,2,3)
– Ledipasvir + Sofosbuvir for 8, 12, or 24 weeks
(a) Treatment-naïve
SOF/LDV
100
94
93
95
98
97
SOF/LDV+RBV
98
99
SVR12 (%)
80
60
40
20
0
8 weeks
12 weeks
Afdhal N, et al NEJM 2014;370:1889-98.
Kowdley K, et al. NEJM 2014; 370:1879-88.
24 weeks
Afdhal N, et al NEJM 2014; 370: 1483-93
Combining 2 or more DAAs will shorten duration
and increase efficacy: Gilead Dual DAA regimen
Phase III studies in non-transplant HCV (ION-1,2,3)
– Ledipasvir + Sofosbuvir for 8, 12, or 24 weeks
(a) Treatment-naïve
(b) Prior Nonresponders
SOF/LDV
SVR12 (%)
100
94
93
95
98
97
SOF/LDV+RBV
98
99
100
80
80
60
60
40
40
20
20
0
0
8 weeks
12 weeks
Afdhal N, et al NEJM 2014;370:1889-98.
Kowdley K, et al. NEJM 2014; 370:1879-88.
24 weeks
94
96
12 weeks
99
99
24 weeks
Afdhal N, et al NEJM 2014; 370: 1483-93
Combining 2 or more DAAs will shorten duration
and increase efficacy: Gilead Dual DAA regimen
Phase III studies in non-transplant HCV (ION-1,2,3)
– Ledipasvir + Sofosbuvir for 8, 12, or 24 weeks
(a) Treatment-naïve
(b) Prior Nonresponders
SOF/LDV
SVR12 (%)
100
94
93
95
98
97
SOF/LDV+RBV
98
99
100
80
80
60
60
40
40
20
20
0
0
8 weeks
12 weeks
Afdhal N, et al NEJM 2014;370:1889-98.
Kowdley K, et al. NEJM 2014; 370:1879-88.
24 weeks
94
96
12 weeks
99
99
24 weeks
Afdhal N, et al NEJM 2014; 370: 1483-93
Other DAA regimens being studied in HCV GT-1:
AbbVie 3D Regimen
1. ABT-450/r
–
–
–
–
NS3/4A macocyclic protease inhibitor
Nanomolar activity against HCV GTs 1-4 and GT6
Once-daily 150mg
Boosted with ritonivir 100mg (co-formulated)
2. Ombitasvir (ABT-267)
– NS5A inhibitor
– Picomolar potency against GTs 1-6
– Once-daily, 25-mg
3. Dasabuvir (ABT-333)
– Non-NUC polymerase inhibitor
– Nanomolar activity against GT 1a and 1b
– Twice daily, 250mg
All DAAs well tolerated in >2000 patients in Phase
1 studies and >2300 patients in Phase 3 studies
35
Other DAA regimens being studied in HCV GT-1:
AbbVie 3D Regimen
Phase III studies in non-cirrhotic HCV
– ABT-450/r+Ombitasvir+Dasabuvir+RBV for 12 wks
(a) SAPPHIRE-1 (n=631)
(b) SAPPHIRE-2 (n=394)
Treatment-naïve, Non-cirrhotic
Non-responder Non-cirrhotic
100
96
95
98
100
80
96
96
97
Overall
GT-1a
GT-1b
80
60
60
40
40
20
20
0
0
Overall
GT-1a
Feld et al. NEJM 2014; ;370:1594-3.
GT-1b
Zeuzem et al. NEJM 2014; ;370:1604-4
Other DAA regimens being studied in HCV GT-1:
AbbVie 3D Regimen
Phase III studies in cirrhotic HCV
– ABT-450/r+Ombitasvir+Dasabuvir+RBV for 12 or 24 wks
(a) TURQUOISE-2: Cirrhotic (n=380)
12 weeks
100
92
93
24 weeks
100
100 100
93
93
80
80
60
40
20
0
Overall
Responder
Relapser
Partial
Responder
Null
Responder
Poordad et al. DOI: 10.1056/NEJMoa1402869
Other DAA regimens being studied in HCV GT-1:
COSMOS: Simeprevir plus sofosbuvir
80 null responders to PR
78% G1a (half with Q80K);
n=14 SMV + SOF
n=27 SMV+ SOF + RBV
SMV 150 mg QD
SOF 400 mg QD
RBV 1000–1200 mg
n=15 SMV + SOF
Results
n=24 SMV + SOF + RBV
Only 3 relapses; 0 SAEs
Non-VF
SVR12
100
4
24-wk Tx
7
4
17
Pts (%)
40
79
93
20
0
100
100
89
80
60
93
100
7
80
96
24 wks
Relaps
e
26/27
13/14
19/24
14/15
SMV/
SOF/RBV
SMV/SOF
SMV/
SOF/RBV
SMV/SOF
SVR12 (%),
non-VF excluded
12-wk Tx
12 wks
60
40
20
0
1
GT 1b
GT 1a
Q80K
absent
GT 1a
Q80K
present
Sulkowski M, et al. EASL 2014, London, O7
SVR Rates in Patients With HCV GT 1
1986 1998
2001 2004 2011
2013 - 14
2015 - 16
100
SVR Rate (%)
80
60
40
20
0
IFN
IFN
24 wks 48 wks
IFN/RBV PEG- TVR/BOC SMV/PEG SOF/RBV SOF/PEG LDV/SOF AbbVie SMV/SOF
48 wks IFN/RBV PEG/RBV /RBV
24 wks
/RBV
FDC 3D+RBV 12 wks
48 wks 48 wks 24 wks
12 wks
8 wks 12 wks
What about Pan-Genotypic DAA regimens?
156 treatment-naive, noncirrhotic GT1-6
– SOF+ new NS5A inhibitor GS-5816 (25mg or100mg)
– 12 weeks, no PEG, no RBV
GS-5816 25 mg/SOF 400 mg
a
b
a.
b.
c.
d.
e.
26/27
d
e
G1 25mg: 1 relapser
G2 25mg: 1 death after EOT
G3 25mg: 1 non-response Wk 8 ; 1 relapser
G3 100mg: 1 reinfection; 1 relapser
G4 100mg: 1 lost to f/u
28/28
GT 1
c
GS-5816 100 mg/SOF 400 mg
10/11
10/10
GT 2
25/27
GT 3
25/27
7/7
6/7
GT 4
1/1
GT 5
4/4
5/5
GT 6
IFN-free, DAA therapy:
What’s coming to clinic in the next 5 years
Wave 1
2013
1.
2.
Simple, shorter therapy for GT-1,4,5,6:
SOF + PEG/RBV for 12 weeks
FDA Dec 2013
First all-oral therapy for GT-2/3:
EMA Jan 2014
SOF + RBV for 12-24 weeks
Wave 2
2014
First all-oral therapy for GT-1:
Gilead LDV/SOF STR for 8 weeks
AbbVie-3D for 12 weeks
NDA Feb 2014
NDA April 2014
Wave 3
2015+
First all-oral pangenotypic therapy:
GS-5816/SOF STR for 8 weeks
NDA Feb 2015?
LDV: ledipasvir formerly GS-5885; STR: single tablet regimen (formerly known as FDC, fixed dose combination);
Ledipasvir and GS-5816 are investigational agents and not approved for use in HCV
What is shortest treatment duration required to
eradicate HCV with 2 DAAs?
Sofosbuvir + Ledipasvir Phase II Programme
% SVR12 (cure)
100%
100%
100%
80%
68%
60%
40%
20%
25/25
25/25
17/25
12 weeks
8 weeks
6 weeks
0%
(1) Gane E. NEJM 2013;368:34–44; (2) Gane E. Gastroenterology 2014;146(3):736-743; (3) Gane E. AASLD 2013:A73. (4) Lawitz E. Lancet
21013 (published on line Nov 5) http://dx.doi.org/10.1016/S0140-6736(13)62121-2;
What is shortest treatment duration required
to eradicate HCV with 3 DAAs?
NIAID Synergy Study: 60 treatment-naïve GT-1
Wk 6
Wk 0
Wk 12
Wk 8
SOF/LDV+GS-9669 (n=20)
SVR12
SOF/LDV+GS-9451 (n=20)
100%
SOF/LDV
SOF/LDV + GS-9669
SOF/LDV + GS-9451
Kohli A, et al. AASLD 2013:. #LB-8
% SVR12 (cure)
Randomized
1:1:1
Open label
SOF/LDV (n=20)
100%
95%
25/2
20/20
5
SOF/LDV
for 12 weeks
19/2
19/20
0
SOF/LDV
+GS-9669
for 6 weeks
100%
80%
60%
40%
20%
0%
20/2
20/20
0
SOF/LDV
+GS-9451
for 6 weeks
Treatment for Chronic HCV beyond 2016
ALL PATIENTS including
• HCV GT 1-6
• BOC/TVR Failures
• Cirrhotic/decompensated
1 pill/day for 6-12 wks
No need for HCV GT, IL28 GT
No on-treatment monitoring
Community prescribing
Treatment uptake
Health burden
l
48 weeks
l
48 weeks
l
6 weeks
Should we treat now or wait?
Should we treat now or wait?
(1) Treat NOW
Affordable
Cure some (40-70%)
Prevent progression
Prevent transmission
Reduce stigma
Poor efficacy
Bad S/E profile
Many CIs
Long duration
LOW UPTAKE
Should we treat now or wait?
(1) Treat LATER
Cure >95%
Little S/Es
No CIs
Short duration
HIGH UPTAKE
COST
Should we treat now or wait?
More expensive DAAs may still be cost-effective
Direct Costs of Telaprevir plus PEG/RBV
• for 48wks treatment = USD90,000 (55K for TVR)
• For S/E = 7-10K per pt
44% SVR (76% if completed 48wks)
Cost per SVR for treatment naïve = 158K
Bichoupan K, et al. AASLD 2013, Washington DC. #244
Direct Costs of Sofosbuvir plus PEG/RBV
• for 12wks treatment = USD94,000 (84K for SOF)
• For S/E = <1K
90% SVR in GT-1
Cost per SVR for treatment naïve = 105K
Should we treat now or wait?
Costs of new DAAs will fall in developing countries
FIERCEPHARMA(http://www.fiercepharma.com)
Gilead in talks with Indian drugmakers to sell
Sovaldi at cut-rate prices
February 4, 2014 | By Tracy Staton
"We are going to give license[s] to Indian companies,"
Gilead is aiming for a price on Sovaldi of about $2,000 for a treatment
course, he said. The U.S. sticker price is $84,000 for a 12-week cycle.
GILEAD OFFERS EGYPT NEW HEPATITIS C DRUG AT
99 PERCENT DISCOUNT
BY MAGGIE FICK CAIRO/LONDON Fri Mar 21, 2014 4:10pm EDT
(Reuters) - Sovaldi, has offered to supply the medicine to Egypt at a 99 percent
discount to the U.S. price.
While the drug will still cost $900 for a 12-week course of treatment, that
is a fraction of the $84,000 charged for a course of treatment in the United
States.
Whom should we treat now?
(a) Those most likely to respond
•
•
•
•
•
•
•
•
•
•
•
EASY TO TREAT
GT2/3
GT1 IL28B CC genotype
GT-1b (protease inhibitors)
No cirrhosis
Treatment-naïve/Relapsers
Low BL viral load
No comorbidities
Younger age
Female
Lower BMI
Caucasian/Asian
BMI = body mass index; BL = baseline; GT = genotype.
DIFFICULT TO TREAT
• GT1, 4
• IL28B non-CC genotype
• GT-1a
• Cirrhosis
• NULL Responders
• High BL viral load
• Comorbidities (e.g. HIV)
• Older age
• Male
• Higher BMI
• Black/Hispanic
Whom should we treat now?
(b) Those with highest risk for complications
1457 untreated HCV+ patients followed for 5 years
– Patients without severe fibrosis had NO liver-related
complications/mortality/transplantation during follow-up
Vergniol J, et al. Gastroenterology 2011; 141: 1970-9
Treatment for Chronic HCV in 2014
CHRONIC HCV
Fibroscan, Biopsy, Fibrotest
Nil or Mild fibrosis
Mod/severe fibrosis, cirrhosis
HCV genotype
GT 1a or 1b
GT 2 or 3
IL28-b genotype
CC
Await IFN-free
DAAs
PEG/RBV RGT
16-24wks
PEG-RBV RGT
24-48wks
CT or TT
Triple therapy
(PI/PEG/RBV)