Transcript The new Treatments - Hepatitis Scotland

The new Treatments
Dr John F Dillon
Curing one person
Curing a population one person at a time
Curing one person
Curing a population one person at a time
2020
2030
3,000
1,000
0
1,000
0
2010
Uptake of therapy by
(up to) 2,000 IDUs per year
2,000
3,000
Uptake of therapy
by 1,000 IDUs per year
2,000
3,000
2,000
1,000
0
Living IDUs with cirrhosis
Uptake of therapy
by 225 IDUs per year
2010
2020
2030
2010
Cirrhosis prevented
Compensated
Decompensated
from antiviral therapy*
cirrhosis
cirrhosis
* Excludes those prevented from antiviral therapy prior to 2008
2020
2030
HCC
SVR = Cure
• SVR rate of 70%
• Means 7 out of 10 people are cured 100% SVR
• 3 out of 10 are not cured 0% SVR
• If we have prediction tools
HCV Therapy
Triple Rx
100%
Protease inhibitor
+ PEG/RBV
24 weeks
PEG/RBV
+ 2nd DAA
12 weeks
90%
Combo DAA
8-12 weeks
No IFN
No RGT
95%
Cure rate
75%
75%
PEG/RBV
48 weeks
50%
IFN/RBV
48 weeks
25%
0%
IFN-α
24 weeks
4%
IFN-α
48 weeks
45%
27%
9%
1985-1989-1991
1998
2003-2011
2014
2015
Genotype 1
Patients with HCV RNA <LLOQ (%)
GT 1, 4, 5, 6 Treatment-Naïve: SOF+PEG-IFN+RBV x 12 Weeks
NEUTRINO Primary Endpoint and Virologic Response
>
299/327
321/325
Week 2
Week 4
On treatment
90
326/327
Week 12/EOT
295/327
Week 12
Post-treatment
 Study met primary endpoint of superiority over historical control rate of 60% (P<0.001)
 Relapse accounted for all virologic failures
 No S282T mutations observed by population or deep sequencing (1% cutoff)
Lawitz E, et al. EASL 2013. Amsterdam, The Netherlands. Oral #1411
Lawitz E, et al. N Engl J Med. 2013 Apr 23 [Epub ahead of print]
HCV1/UK/13-05/ABAR/1201c
Error bars represent 95% confidence intervals
QUEST-1: Phase 3 trial of Simeprevir + PR in
G1 treatment-naive patients
Response Guided Therapy
criteria met by 85%
SVR in 91% of RGT patients
No incremental rash/anemia
Hyperbilrubinemia
A NS3a PI a replacement for Boceprevir or telaprevir
Jacobson IM et al, EASL 2013, Amsterdam, #1425
10
NUC NS5B inhibitor sofosbuvir & Daclatasvir ±
Ribavirin (geno 1, n =45)
% undetectable HCV RNA
GS7977/daclatasvir
100%
80%
93%
79%
GS7977/daclatasvir/RBV
100%
93%
100%100%
100%100%
77%
67%
60%
40%
20%
0%
2 weeks
On Rx
4 weeks
On Rx
12 weeks 24 weeks 12 weeks
On Rx End of Rx post-Rx
Sulkowski M, et al. J Hepatol 2012; 56: S1422
AbbVie Phase III Clinical Program Results
fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) twice daily
Study
PEARL-II
(12 weeks)
PEARL-III
(12 weeks)
PEARL-IV
(12 weeks)
TURQUOISE-II
(12 & 24 weeks)
SAPPHIRE-I
(12 weeks)
SAPPHIRE-II
(12 weeks)
Patients
Treatment Regimen
AbbVie regimen + RBV
GT1b treatment(n=88)
experienced
AbbVie regimen only
(N=179)
(n=91)
AbbVie regimen + RBV
GT1b treatment-naive
(n=210)
(N=419)
AbbVie regimen only
(n=209)
AbbVie regimen + RBV
GT1a treatment-naive
(n=100)
(N=305)
AbbVie regimen only
(n=205)
GT1 treatment-naive
AbbVie regimen + RBV, 12
and treatment-experienced weeks (n=208)
with
AbbVie regimen + RBV, 24
compensated cirrhosis
weeks (n=172)
(N=380)
GT1 treatment-naive
AbbVie regimen + RBV
(N=631)
(n=473)
GT1 treatment-experienced AbbVie regimen + RBV
(N=394)
(n=297)
SVR12
97%
(85/88)
100%
(91/91)
99%
(209/210)
99%
(207/209)
97%
(97/100)
90%
(185/205)
92%
(191/208)
96%
(165/172)
96%
(455/473)
96%
(286/297)
Genotype 3
The new tough kid on the block
SVR12 Rates Across SOF-Based Studies
HCV GT 3 Patients
Noncirrhotic
Cirrhotic
Treatment-Experienced
Treatment-Naïve
94%
92%
87%
100%
(%)
80%
SVR12
63%
60%
68%
61%
61%
83%
83%
10/12
10/12
60%
34%
21%
40%
20%
89/145
0%
13/38
57/84
3/14
86/92
12/13
FISSION
POSITRON
VALENCE
SOF + RBV 12 wk SOF + RBV 12 wk SOF + RBV 24 wk
25/40
14/23
FUSION
SOF RBV 16 wk
87/100
27/45
VALENCE
SOF + RBV 24 wk
LONESTAR-2
SOF + PegIFN + RBV
12 wk
HCV GT 3 patients treated with SOF + RBV for 24 weeks or SOF + RBV + PegIFN for 12
weeks achieved high SVR rates regardless of presence of cirrhosis or treatment experience
Lawitz E, et al. N Engl J Med. 2013 May 16;368(20):1878-87. Zeuzem S, et al. AASLD 2013. Washington, DC. #1085.
Jacobson IM, et al. N Engl J Med. 2013 May 16;368(20):1867-77. Lawitz E, et al. AASLD 2013. Washington, DC. Oral #LB-4.
NS3/NS4A PROTEASE INHIBITORS
 BOCEPREVIR
 TELAPREVIR
 SIMEPREVIR
 FALDAPREVIR
 VANIPREVIR (MK-7009)
 DANOPREVIR
 ASUNAPREVIR
 ABT-450
 MK-5172
 SOLAPREVIR
 GS-9451
POLYMERASE INHIBITORS (NS5b)
• NUCLEOSIDE
– MERICITABINE
• NUCLEOTIDE
– SOFOSBUVIR
– VX-135
• NON-NUC’s
– ABT-072
– ABT-333
– BI-207127
NS5A COMPLEX INHIBITORS
•
•
•
•
•
•
DACLATASVIR
ABT-267
LEDIPASVIR
MK-8742
ACH-3102
PP-1668
CYCLOPHILIN INHIBITORS
• ALISPORIVIR
TLR7-INHIBITOR
• GS-9620
NOVEL INTERFERONS
• LAMBDA-IFN
Future treatment
Genotype 1
Genotype 3
• SVR better than 90% with
• SVR about 90%
• 2 or 3 oral drugs for 8-12 weeks
• OR
• Interferon plus 1 or 2 drugs for 12
weeks
• Interferon plus 2 oral drugs 12
weeks
• 2 or 3 Oral drugs 24 weeks
• With Prediction
• Interferon/ribavirin 16 weeks
So back to treating one person
• The new treatments are much more expensive
• SO
• Get a lot more money?
• In Scotland there will be some new money
• Treat a lot less people?
• Use some of the old treatments in some people.
• Including a bit of Interferon