the new treatments dr john f dillon. curing one person curing a population one person at a time
TRANSCRIPT
The new TreatmentsDr John F Dillon
Curing one person Curing a population one person at a time
Cirrhosis prevented
from antiviral therapy*
Livi
ng ID
Us
with
cirr
hosi
s
2010 2020 2030
01,
000
2,00
03,
000
2010 2020 20300
1,00
02,
000
3,00
02010 2020 2030
01,
000
2,00
03,
000
Decompensated
cirrhosisHCC
* Excludes those prevented from antiviral therapy prior to 2008
Compensated
cirrhosis
Uptake of therapy
by 225 IDUs per year
Uptake of therapy
by 1,000 IDUs per year
Uptake of therapy by
(up to) 2,000 IDUs per year
Curing one person Curing a population one person at a time
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
1985-1989-1991
HCV Therapy
0%
25%
50%
75%
100%Cu
re ra
te
IFN-α48 weeks
9%
IFN-α24 weeks
4%
IFN/RBV 48 weeks
27%
PEG/RBV 48 weeks
45%
Triple RxProtease inhibitor
+ PEG/RBV24 weeks
75%
2003-2011
PEG/RBV+ 2nd DAA12 weeks
90%
20141998
Combo DAA8-12 weeks
No IFNNo RGT
95%
2015
Genotype 1
Error bars represent 95% confidence intervals
GT 1, 4, 5, 6 Treatment-Naïve: SOF+PEG-IFN+RBV x 12 WeeksNEUTRINO Primary Endpoint and Virologic Response
¨ Study met primary endpoint of superiority over historical control rate of 60% (P<0.001)On treatment
299/327 321/325 326/327
Week 2 Week 4 Week 12/EOT
Pat
ien
ts w
ith
HC
V R
NA
<L
LO
Q
(%)
90
Post-treatment
Week 12
295/327
Lawitz E, et al. EASL 2013. Amsterdam, The Netherlands. Oral #1411Lawitz E, et al. N Engl J Med. 2013 Apr 23 [Epub ahead of print]
¨ Relapse accounted for all virologic failures¨ No S282T mutations observed by population or deep sequencing (1% cutoff)
>
HCV1/UK/13-05/ABAR/1201c
QUEST-1: Phase 3 trial of Simeprevir + PR in G1 treatment-naive patients
10Jacobson IM et al, EASL 2013, Amsterdam, #1425
A NS3a PI a replacement for Boceprevir or telaprevir
Response Guided Therapycriteria met by 85%SVR in 91% of RGT patientsNo incremental rash/anemiaHyperbilrubinemia
Sulkowski M, et al. J Hepatol 2012; 56: S1422
NUC NS5B inhibitor sofosbuvir & Daclatasvir ± Ribavirin (geno 1, n =45)
79%
93% 93%100% 100%
67%77%
100%100% 100%
0%
20%
40%
60%
80%
100%
2 weeksOn Rx
4 weeksOn Rx
12 weeksOn Rx
24 weeksEnd of Rx
12 weekspost-Rx
% u
ndet
ecta
ble
HC
V R
NA
GS7977/daclatasvir GS7977/daclatasvir/RBV
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 Patients Treatment Regimen SVR12
PEARL-II(12 weeks)
GT1b treatment-experienced(N=179)
AbbVie regimen + RBV (n=88)
97%(85/88)
AbbVie regimen only (n=91)
100%(91/91)
PEARL-III(12 weeks)
GT1b treatment-naive(N=419)
AbbVie regimen + RBV (n=210)
99%(209/210)
AbbVie regimen only (n=209)
99%(207/209)
PEARL-IV(12 weeks)
GT1a treatment-naive (N=305)
AbbVie regimen + RBV (n=100)
97%(97/100)
AbbVie regimen only (n=205)
90%(185/205)
TURQUOISE-II(12 & 24 weeks)
GT1 treatment-naive and treatment-experienced with compensated cirrhosis(N=380)
AbbVie regimen + RBV, 12 weeks (n=208)
92% (191/208)
AbbVie regimen + RBV, 24 weeks (n=172)
96%(165/172)
SAPPHIRE-I(12 weeks)
GT1 treatment-naive(N=631)
AbbVie regimen + RBV (n=473)
96%(455/473)
SAPPHIRE-II(12 weeks)
GT1 treatment-experienced(N=394)
AbbVie regimen + RBV (n=297)
96%(286/297)
Genotype 3The new tough kid on the block
SVR12 Rates Across SOF-Based Studies HCV GT 3 Patients
Treatment-Naïve Treatment-Experienced
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.
Noncirrhotic Cirrhotic
61%
87%
60%
SV
R12
(%
)
89/145 86/92
FUSION SOF RBV 16 wk
VALENCESOF + RBV 24 wk
LONESTAR-2SOF + PegIFN + RBV
12 wk
87/10014/23
83%
10/12
92%94%
12/13 25/40
63%
27/45
83%
10/12
68%
21%
61%
34%
0%
20%
40%
60%
80%
100%
FISSIONSOF + RBV 12 wk
VALENCESOF + RBV 24 wk
13/38
POSITRONSOF + RBV 12 wk
57/84 3/14
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
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• SVR better than 90% with
• 2 or 3 oral drugs for 8-12 weeks• OR• Interferon plus 1 or 2 drugs for 12
weeks
Genotype 3• SVR about 90%
• 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