f/c aetc faculty hiv/hcv thursday may 8, 2014 | 1:30- 2:30pm (edt) facilitator/ presenter dushyantha...
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F/C AETC FacultyHIV/HCV
Thursday May 8, 2014 | 1:30- 2:30pm (EDT)
Facilitator/ PresenterDushyantha T. Jayaweera, MD, MRCOG (UK), FACP
University of Miami
Case DiscussantPatrick Marsh, MD
University of South Florida
Maribel Gonzalez, RN, ARNPUniversity of South Florida
HIV Case Conference:Highlights from EASL
Dushyantha T. Jayaweera MD, MRCOG (UK), FACP
Associate Vice Provost for Human Subject Research & Professor of Medicine, University of Miami, Miller School of Medicine, Division of Infectious DiseasesFaculty Member, Florida/Caribbean AIDS Education and Training Center
HCV TREATMENT IN TREATMENT NAIVE PATIENTS
SAPPHIRE-I Study: Design
0 12 24
ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bid ABT-333 bid + RBV bid
(n=473)(n=473)
ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bid ABT-333 bid + RBV bid
(n=473)(n=473)
Placebo*Placebo*(n=158)(n=158)
Placebo*Placebo*(n=158)(n=158)
Week
ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bidABT-333 bid + RBV bid
(n=158)(n=158)
ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bidABT-333 bid + RBV bid
(n=158)(n=158)
Double-Blind
Open-Label
Feld J, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O60.
Phase 3 StudyDouble-Blind
Key eligibility criteria•HCV genotype 1•Treatment-naïve•No cirrhosis •No HIV or HBV
SAPPHIRE-1 Study: Interim Results
• Virologic relapse: 1.7%
• 3D regimen + RBV was well-tolerated
• Discontinuations due to adverse events: 0.6%
• Most commonly reported adverse events
• Fatigue
• Headache
• Nausea
Feld J, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O60.
0
20
40
60
80
100
Pat
ien
ts
(Per
cen
tag
e)
SVR12 Rates3D Regimen + RBV
1a(n=322)
1b(n=151)
Overall(n=473)
95%98%96%
Genotype
0 12 24
ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV bid
(n=210)
ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV bid
(n=210)
ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV Placebo
(n=209)
ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV Placebo
(n=209)
Week
Phase 3 StudyDouble-Blind
Placebo-controlled
Key eligibility criteria•HCV genotype 1•Treatment-naïve•No cirrhosis •No HIV or HBV
PEARL-III Study: Design
Ferenci P, et al. 49th EASL; London, England; April 9-13, 2014. Abst. P1299.
Pearl-III Study: SVR12 and Virologic Failure Rates
3D Regimen + RBV
Ferenci P, et al. 49th EASL; London, England; April 9-13, 2014. Abst. P1299.
0
20
40
60
80
100
Pat
ien
ts (
Per
cen
tag
e)
No RBV(n=209)
With RBV(n=210)
99%99%
SVR12
0%No RBV(n=209)
0.5%With RBV
(n=210)
Virologic Failure
Pearl-III Study: Safety Results
• 3D regimen + RBV was well tolerated• Discontinuations due to adverse events
• With RBV: 0%• No RBV: 0%
• Most commonly reported adverse events• Headache• Fatigue
Ferenci P, et al. 49th EASL; London, England; April 9-13, 2014. Abst.
P1299.
ION-1 Study: Design
• GT 1 HCV treatment-naïve patients in Europe and USA• Broad inclusion criteria
• Targeted 20% enrollment of patients with cirrhosis• No upper age or BMI limit• Platelet count ≥50,000/mm3, no neutrophil minimum
• 865 patients randomized 1:1:1:1 across four arms • Stratified by HCV subtype (1a or 1b) and cirrhosis
Mangia A, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O164.
Wk 0 Wk 12 Wk 36Wk 24
LDV/SOF LDV/SOF SVR12
LDV/SOF + RBV LDV/SOF + RBV
LDV/SOF LDV/SOF
LDV/SOF + RBV LDV/SOF + RBV
SVR12
SVR12
SVR12
99 97 98 9994 100 94 100
179/180 32/34 178/184 33/33 181/184 31/33 179/181 36/36
12 Weeks 24 Weeks
LDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF
SV
R12
(P
erc
en
tag
e)
Absence of Cirrhosis Cirrhosis
ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis
Error bars represent 95% confidence intervals.
Mangia A, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O164.
179/180 32/34 178/184 33/33 181/184 31/33 179/181 36/36
12 Weeks 24 Weeks
LDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF
SV
R12
(P
erc
en
tag
e)
Absence of Cirrhosis Cirrhosis
ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis
Error bars represent 95% confidence intervals.
Mangia A, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O164.
ION-3 Study: Design
• GT 1 treatment-naïve patients without cirrhosis• Broad inclusion criteria
• No upper age or BMI limit• Opiate substitution therapy allowed
• 647 patients randomized 1:1:1 across three arms• Stratified by HCV subtype (1a or 1b)
LDV/SOF LDV/SOF
LDV/SOF LDV/SOF
LDV/SOF + RBV LDV/SOF + RBV
SVR12
SVR12
SVR12
Kowdley K, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O56.
Wk 0 Wk 12 Wk 36Wk 24
Error bars represent 95% confidence intervals.
Kowdley K, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O56.
ION-3 Study Results – Non-Inferiority Comparison
201/216202/215 206/216
p=0.52
8 Weeks 12 Weeks
LDV/SOF + RBVLDV/SOF LDV/SOF
SV
R12
(P
erc
en
tag
e)
Study Design: MK-5172 (100 mg QD) + MK-8742 (50 mg QD) ± RBV in 253 Pte
n = 31Follow-up
Follow-up
Follow-up
Follow-up
D1 TW12 SVR12TW4 TW8
TN
+ C
irrh
osi
sn
=12
3T
N +
Cir
rho
sis
n=
123
PR
-Nu
lls ±
Cir
rho
sis
n=
130
PR
-Nu
lls ±
Cir
rho
sis
n=
130
SVR24TW18 FU8FU4
Follow-up
Follow-up
Follow-up
No RBVNo RBV
+ RBV+ RBV+ RBV+ RBV
No RBVNo RBV
+ RBV+ RBV+ RBV+ RBV
+ RBV+ RBV+ RBV+ RBV
No RBVNo RBVNo RBVNo RBV
No RBVNo RBVNo RBVNo RBV
+ RBV+ RBV+ RBV+ RBV Follow-up
n = 29
n = 32
n = 31
n = 32
n = 33
n = 33
n = 32
Lawitz E, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O61.
No RBVNo RBV
+ RBV+ RBV+ RBV+ RBV
No RBVNo RBV
+ RBV+ RBV+ RBV+ RBV
+ RBV+ RBV+ RBV+ RBV
No RBVNo RBVNo RBVNo RBV
No RBVNo RBVNo RBVNo RBV
+ RBV+ RBV+ RBV+ RBV
2831
2831
32 32
2929
3031
3131
31 32
2929
2831
2930*
30 31*
2829
TW4 TW12 FU4/8
Breakthrough
Relapse
Discontinuation
Efficacy of MK-5172 + MK-8742 ± RBVin Treat-Naïve Pte + Cirrhosis:12W vs18W
• *Excludes patients who have not yet reached the FU4 time point• 12 week arms include 97% of FU8 results
Lawitz E, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O61.
Discussion