Transcript Option A - IC-HEP

Darrell Crawford, MD
Brisbane, Australia
This activity has been supported by an independent
medical education grant from Bristol Myers Squibb.
2013 IC-HEP Educational supporters include Bristol Myers Squibb and Janssen Therapeutics
EMEA. Supporters do not influence IC-HEP faculty selection or educational content.
1
Phase 2b study of the interferon-free and ribavirin-free combination of
daclatasvir, asunaprevir, and BMS-791325 for 12 weeks in treatment-naïve
patients with chronic HCV genotype 1 infection
Gregory T. Everson1, Karen D. Sims2, Paul J. Thuluvath3, Eric Lawitz4, Tarek Hassanein5,
Maribel Rodriguez-Torres6, Trevor Hawkins7, Howard Schwartz8, Vinod K. Rustgi9, Federico Hinestrosa10,
James M. Levin11, Zobair M. Younossi12, Lynn R. Webster13, Timothy Eley2, Shu-Pang Huang14,
Fiona McPhee15, Dennis M. Grasela2, David F. Gardiner2
1. University of Colorado Denver, Aurora, CO, United States.
2. Bristol-Myers Squibb, Hopewell, NJ, United States.
3. Mercy Medical Center, Baltimore, MD, United States.
4. The Texas Liver Institute, University of Texas Health Science
Center, San Antonio, TX, United States.
5. Southern California Liver Centers, Coronado, CA, United States.
6. Fundación de Investigación, San Juan, Puerto Rico,
United States.
7. Southwest CARE Center, Santa Fe, NM, United States.
8. Miami Research Associates, South Miami, FL, United States.
9. Metropolitan Research, Arlington, VA, United States.
10. Orlando Immunology Center, Orlando, FL, United States.
11. Dean Foundation for Health, Research and Education, Inc,
Madison, WI, United States.
12. Inova Fairfax Hospital, Center for Liver Diseases,
Falls Church, VA, United States.
13. CRI Lifetree, Salt Lake City, UT, United States.
14. Bristol-Myers Squibb, Princeton, NJ, United States.
15. Bristol-Myers Squibb, Wallingford, CT, United States.
2
•
Daclatasvir (DCV)
– NS5A replication complex inhibitor with potent, pan-genotypic activity in vitro
– Studied in over 5500 patients
•
Asunaprevir (ASV)
– NS3 protease inhibitor active against genotypes (GT) 1, 4, 5, and 6 in vitro
– Studied in over 2000 patients
•
BMS-791325
– Non-nucleoside, NS5B polymerase inhibitor active against GT 1, 3, 4, 5, and 6
in vitro
– Studied in over 500 patients
3
Primary endpoint: SVR12
N = 80
DCV 30 mg BID +
ASV 200 mg BID +
BMS-791325 75 mg BID
N = 86
DCV 30 mg BID +
ASV 200 mg BID +
BMS-791325 150 mg BID
12-week follow-up
Week 0
12
Additional
follow-up to
SVR48
24
•
Patients: treatment-naive, stratified by GT 1a/1b and presence of biopsy-confirmed cirrhosis
(82% GT1a and 9% cirrhotics).
•
Primary end point: HCV RNA < LLOQ 12 weeks post-treatment (SVR12)
– Observed analysis: breakthrough, relapse, addition of pegIFNα/RBV = failure
– Modified intent-to-treat analysis: missing, breakthrough, relapse or addition of pegIFNα/RBV = failure
4
Response, % of patients
100
97.5
94.2
92.4
91.7
92.2
91.7
80
60
DCV + ASV +
‘325 75 mg
40
DCV + ASV +
‘325 150 mg
20
0
78/80
81/86
End of Treatment
73/79
77/84
SVR4
71/77
77/84
SVR12
5
Event, n (%)
Serious AEs
AEs leading to discontinuation
Grade 3/4 AEs
Most frequent on-treatment AEs (≥ 10%)
Headache
Diarrhea
Fatigue
Nausea
Grade 3/4 lab abnormalities
Aspartate aminotransferase (AST)
Glucose, fasting serum (high)
Phosphorus, inorganic
Bilirubin, total
DCV + ASV +
‘325 75 mg
N = 80
DCV + ASV +
‘325 150 mg
N = 86
Total
N = 166
1 (1.3)
1 (1.3)
0
2 (2.3)
1 (1.2)
1 (1.2)
3 (1.6)
2 (1.1)
1 (0.5)
17 (21.3)
12 (15.0)
12 (15.0)
10 (12.5)
24 (27.9)
13 (15.1)
7 (8.1)
7 (8.1)
41 (24.7)
25 (15.1)
19 (11.4)
17 (10.2)
1 (1.3)
1 (1.3)
0
0
0
1 (1.2)
1 (1.2)
1 (1.2)
1 (0.5)
2 (1.2)
1 (0.5)
1 (0.5)
6
All-oral Combination of Daclatasvir Plus Asunaprevir in
Interferon Ineligible Naive/Intolerant and Nonresponder
Japanese Patients Chronically Infected with HCV
Genotype 1b: Results from a Phase 3 Trial
Kazuaki Chayama1, Yoshiyuki Suzuki2, Kenji Ikeda2, Joji Toyota3, Yoshiyasu Karino3, Yoshiiku Kawakami1, Akio Ido4, Kazuhide
Yamamoto5, Koichi Takaguchi6, Namiki Izumi7, Kazuhiko Koike8, Tetsuo Takehara9, Norifumi Kawada10, Michio Sata11,
Hidetaka Miyagoshi12, Timothy Eley13, Fiona McPhee13, Wenhua Hu13, Hiroki Ishikawa12, Eric A. Hughes13, Hiromitsu Kumada2
1. Hiroshima University, Hiroshima, Japan.
2. Toranomon Hospital, Tokyo, Japan.
3. Sapporo-Kousei General Hospital, Sapporo, Japan.
4. Kagoshima University, Kagoshima, Japan.
5. Okayama University, Okayama, Japan.
6. Kagawa Prefectural Hospital, Kagawa, Japan.
7. Musashino Red Cross Hospital, Tokyo, Japan.
8. University of Tokyo, Tokyo, Japan.
9. Osaka University, Osaka, Japan.
10. Osaka City University, Osaka, Japan.
11. Kurume University, Fukuoka, Japan.
12. Bristol-Myers KK, Tokyo, Japan.
13. Bristol-Myers Squibb, Princeton, NJ, United States.
7
HCV RNA < LLOQ, n (%)
Ineligible naïve/Intolerant
(IN/I) Patients
n = 135a
Nonresponder (NR)
Patients
n = 87b
Total
N = 222
RVR, Week 4
114 (84.4)
53 (60.9)
167 (75.2)
cEVR, Week 12
125 (92.6)
77 (88.5)
202 (91.0)
SVR4
126 (93.3)
71 (81.6)
197 (88.7)
SVR12
120 (88.9)
70 (80.5)
190 (85.6)
SVR24
118 (87.4)
70 (80.5)
188 (84.7)
aIneligible
bNull
naïve: n=100; Intolerant: n=35
responders: n=48; Partial responders: n=36; Undetermined: n=3
8
Once Daily Sofosbuvir/Ledipasvir Fixed Dose Combination
with or without Ribavirin: the ELECTRON trial
Edward J. Gane1, Catherine A. Stedman2, Robert H. Hyland3, Xiao Ding3,
Evguenia S. Svarovskaia3, Phil S. Pang3, William T. Symonds3
1. Auckland Clinical Studies, Auckland, New Zealand.
2. Christchurch Clinical Studies Trust, Christchurch, New Zealand.
3. Gilead Science, Inc, Foster City, CA, United States.
9
Sofosbuvir/Ledipasvir FDC
• Once daily, oral fixed-dose (400/90 mg)
combination tablet
• No food effect
• >2000 patients treated
SOF
Nucleotide
Polymerase
inhibitor
LDV
NS5A
inhibitor
GS-9669
• HCV NS5B non-nucleoside inhibitor, binding at thumb site II of the polymerase
• Potent antiviral activity with QD dosing
• Nanomolar potency against GT 1a and 1b
10
F4
GT 1
Experienced
F3/F4
GT 1 Naïve
F0/F1/F2
Randomized Randomized
Wk 0
Wk 6
Wk 12
SOF/LDV FDC (n=10)
SOF/LDV FDC + RBV (n=10)
SOF/LDV FDC + RBV (n=25)
SVR12
SOF/LDV FDC + GS-9669 (n=25)
SOF/LDV FDC + RBV (n=25)
• Primary endpoint: SVR12 (HCV RNA <LLOQ)
• Patients enrolled in ELECTRON or ELECTRON 2 (GT1, F3/F4)
• All groups were open label
11
SVR 12 (%)
100
90
80
70
60
50
40
30
20
10
0
Duration (wk)
100
100
100
7/10
9/9
25/25*
26/26*
SOF/LDV
SOF/LDV + RBV
SOF/LDV + RBV
SOF/LDV + GS9669
12
12
12
12
70
F4 only
F3/F4
12
SVR 12 (%)
100
90
80
70
60
50
40
30
20
10
0
Duration (wk)
100
100
68
25/25
21/21
17/25
SOF + LDV + RBV*
SOF/LDV + RBV †
SOF/LDV + RBV
12
8
6
*Gane et al. EASL 2013. †Lawitz et al, Abstract #215, AASLD 2013 (LONESTAR)
Gane EJ, et al. Abstract #73, AASLD 2013
13
• In treatment-experienced patients with advanced
fibrosis/cirrhosis, either RBV or GS-9669 may
enhance the efficacy of SOF/LDV given for 12 weeks
• The optimal duration of SOF/LDV in treatment-naïve
GT 1 patients, even with the addition of RBV, is more
than 6 weeks
• Regimens of SOF/LDV alone, or with RBV or GS-
9669, were safe and well tolerated
14
Interferon- and Ribavirin-free Regimen of ABT-450/r + ABT-267
in HCV Genotype 1b-infected Treatment-naïve Patients and
Prior Null Responders
Eric Lawitz1, Christophe Hezode2, Peter Varunok3, Paul J. Thuluvath4, Tolga Baykal5, Mudra Kapoor5,
Sandra S. Lovell5, Tianli Wang5, Tami Pilot-Matias5, Regis A. Vilchez5, Barry Bernstein5
1. The Texas Liver Institute, University of Texas Health Science Center,
San Antonio, TX, United States.
2. Assistance Publique Hopitaux de Paris, Paris, France.
3. Premier Medical Group of the Hudson Valley, PC, Poughkeepsie, NY, United States.
4. The Institute for Digestive Health and Liver Disease at Mercy, Baltimore, MD, United States.
5. AbbVie Inc., North Chicago, IL, United States.
15
• ABT-450 is an HCV protease inhibitor
(dosed with ritonavir 100 mg, ABT-450/r)
• ABT-267 is an NS5A inhibitor
• Both compounds have shown potent antiviral
activity in vitro against HCV genotypes (GT)
1-4 and 6.
Lawitz E, et al. Abstract #75, AASLD 2013
16
Planned HCV Genotype/Regimen
N BL Treatment Experience Week 12
Group 1 40
Substudy 1:
Patients
Without
Cirrhosis
Group 2 40
Group 3 40
Group 4 40
Group 5 40
Group 6 40
Substudy 2: Group 7 40
Patients With
Compensated Group 8 40
Cirrhosis
Week 24
GT4 ABT-450/r + ABT-267
Treatment-naïve
GT1b ABT-450/r + ABT-267
Treatment-naïve
GT1b ABT-450/r + ABT-267
Null Responders
GT4 ABT-450/r + ABT-267 + rbv
Treatment-naïve
GT4 ABT-450/r + ABT-267
Partial/Null Responders & Relapsers
GT4 ABT-450/r + ABT-267 + rbv
Partial/Null Responders & Relapsers
GT1b ABT-450/r + ABT-267
Treatment-naïve
GT1b ABT-450/r + ABT-267
Partial/Null Responders & Relapsers
Lawitz E, et al. Abstract #75, AASLD 2013
17
Percentage of Patients (%)
100
97.6
97.6
95.2
42/42
41/42
41/42
40/42
Week 4
Week 12
(EOTR)
100
80
60
40
20
0
SVR4
SVR12
Lawitz E, et al. Abstract #75, AASLD 2013
18
Percentage of Patients (%)
100
97.5
97.5
39/40
39/40
92.5
90.0
37/40
36/40
80
60
40
20
0
Week 4
Week 12
(EOTR)
SVR4
SVR12
Lawitz E, et al. Abstract #75, AASLD 2013
19
GT1b-infected
Treatment-naïve Patients
(N=42)
GT1b-infected
Prior Null Responders
(N=40)
Headache
14 (33.3)
10 (25.0)
Nausea
8 (19.0)
0
Dry Skin
7 (16.7)
0
Fatigue
6 (14.3)
0
Pruritus
6 (14.3)
0
Diarrhea
6 (14.3)
0
Event, n (%)
Lawitz E, et al. Abstract #75, AASLD 2013
20
Sofosbuvir in Combination With PegIFN and Ribavirin for 12 Weeks
Provides High SVR Rates in HCV-Infected Genotype 2 or 3 Treatment
Experienced Patients with and without Compensated Cirrhosis:
Results from the LONESTAR-2 Study
Eric Lawitz1, 2, Fred Poordad1, 2, Diana M. Brainard3, Robert H. Hyland3, Di An3,
William T. Symonds3, John G. McHutchison3, Fernando E. Membreno1, 2
1. Texas Liver Institute, San Antonio, TX, United States.
2. University of Texas Health Science Center, San Antonio, TX, United States.
3. Gilead Science, Inc, Foster City, CA, United States.
21
Wk 0
GT 2/3
(N=47)
•
Wk 12
SOF + PEG/RBV
Wk 24
Wk 36
SVR12
Study population
– HCV GT 2 or 3
– Failed treatment with pegylated interferon and ribavirin
– Approximately 50% with compensated cirrhosis
– HIV and HBV coinfected patients excluded
Lawitz E, et al. Abstract #LB-4, AASLD 2013
22
100
89
96
83
SVR12
(%)
80
60
40
20
0
42/47
22/23
20/24
Overall
GT 2
GT 3
Lawitz E, et al. Abstract #LB-4, AASLD 2013
23
No Cirrhosis
SVR12 (%)
100
Cirrhosis
100
93
83
83
9/9
13/14
10/12
10/12
80
60
40
20
0
GT 2
GT 3
Error bars represent 95% confidence intervals.
Lawitz E, et al. Abstract #LB-4, AASLD 2013
24
Patients, n (%)
Overall
safety
Hematologic
abnormalities
SOF + PEG/RBV
12 weeks
(N=47)
AEs
45 (96)
Grade 3-4 AEs
15 (32)
Serious AEs
4 (9)
Treatment discontinuation due to AEs
2 (4)
Grade 3-4 laboratory abnormality
28 (60)
Hemoglobin <10 g/dL
13 (28)
Hemoglobin <8.5 g/dL
4 (9)
Absolute neutrophil count <750/mm3
13 (28)
Platelets <50,000/mm3
7 (15)
Lawitz E, et al. Abstract #LB-4, AASLD 2013
25
• SOF + PEG/RBV for 12 weeks demonstrated high efficacy in
treatment-experienced GT 2/3 patients who have historically low
response rates and limited treatment options
– SVR rates were similar in patients with and without cirrhosis
• SOF + PEG/RBV was generally safe and well tolerated
– Safety profile consistent with PEG/RBV treatment
– Low discontinuation rates
Lawitz E, et al. Abstract #LB-4, AASLD 2013
26
Sofosbuvir + Ribavirin for 12 or 24 Weeks for Patients with
HCV Genotype 2 or 3: the VALENCE trial
Stefan Zeuzem1, Geoffrey M. Dusheiko2, Riina Salupere3, Alessandra Mangia4, Robert Flisiak5, Robert H.
Hyland6, Ari Illeperuma6, Evguenia S. Svarovskaia6, Diana M. Brainard6, William T. Symonds6, John G.
McHutchison6, Ola Weiland7, Hendrik W. Reesink8, Peter Ferenci9, Christophe Hezode10, Rafael Esteban11
1. Johann Wolfgang Goethe University, Frankfurt, Germany.
2. Royal Free and University College School of Medicine,
Royal Free Hospital, London, United Kingdom.
3. Tartu University Hospital, Tartu, Estonia.
4. "Casa Sollievo della Sofferenza" Hospital, San Giovanni
Rotondo, Italy.
5. Medical University of Bialystok, Bialystok, Poland.
6. Gilead Sciences, Inc., Foster City, CA, United States.
7. Karolinska Institutet, Karolinska University Hospital
Huddinge, Stockholm, Sweden.
8. Academic Medical Center, Amsterdam, Netherlands.
9. Medical University of Vienna, Vienna, Austria.
10. Hôpital Henri Mondor, Créteil, France.
11. Hospital Universitario Val d’Hebron, Barcelona, Spain.
27
Wk 0
Wk 12
Wk 24
SVR4, SVR12,
SVR24
Placebo*
(n = 85)
Sofosbuvir + Ribavirin
(n = 84)*
Sofosbuvir + Ribavirin
(n = 250)
*Protocol amended to eliminate placebo arm and to extend treatment duration to 24 weeks
for patients with genotype 3 HCV irrespective of prior treatment history.
Zeuzem S, et al. Abstract #1085, AASLD 2013
28
SVR12 in GT 2 Patients Treated
for 12 Weeks
SVR12 in GT 2 and
3 Patients*
100
100
93
97
100
91
88
85
80
SVR12 (%)
SVR12 (%)
80
60
40
60
40
20
20
68/73
212/
250
GT 2
SOF+RBV 12 wk
GT 3
SOF+RBV 24 wk
0
29/30
0
Naïve,
Noncirrhotic
2/
2
Naïve,
Cirrhotic
30/33
Experienced,
Noncirrhotic
7/
8
Experienced,
Cirrhotic
*3 of 11 patients (27%) with HCV GT 3 who received 12 weeks of SOF+RBV achieved SVR 12.
Zeuzem S, et al. Abstract #1085, AASLD 2013
29
100
94
92
87
SVR12 (%)
80
60
60
40
20
0
86/92
12/13
87/100
27/45
Naïve,
Noncirrhotic
Naïve,
Cirrhotic
Experienced,
Noncirrhotic
Experienced,
Cirrhotic
Zeuzem S, et al. Abstract #1085, AASLD 2013
30
All-Oral Therapy With Sofosbuvir Plus Ribavirin For the
Treatment of HCV Genotype 1, 2, and 3 Infection in Patients
Co-infected With HIV (PHOTON-1)
Mark S. Sulkowski1, Maribel Rodriguez-Torres2, Jacob P. Lalezari3, W. Jeffrey Fessel4, Karam Mounzer5,
Margaret C. Shuhart6, Anne Luetkemeyer7, David M. Asmuth8, Anuj Gaggar9, William T. Symonds9, John G.
McHutchison9, Susanna Naggie10, Douglas T. Dieterich11
1. Johns Hopkins Medical Center, Baltimore, MD, United States.
2. Fundacion De Investigacion, San Juan, Puerto Rico, United States.
3. Quest Clinical Research, San Francisco, CA, United States.
4. Kaiser Permanente, San Francisco, CA, United States.
5. Philadelphia FIGHT, Philadelphia, PA, United States.
6. Harborview Medical Center, Seattle, WA, United States.
7. San Francisco General Hospital, San Francisco, CA, United States.
8. University of California Davis Medical Center, Sacramento, CA, United States.
9. Gilead Sciences, Inc., Foster City, CA, United States.
10. Duke Clinical Research Institute, Durham, NC, United States.
11. Mount Sinai School of Medicine, New York, NY, United States.
31
36
Wk 0
GT 1
TN
Wk 12
Wk 24
Wk 36
SVR12
SOF + RBV, n=114
GT 2/3 TN
SOF + RBV, n=68
GT 2/3 TE
SOF + RBV, n=41
SVR12
SVR12
• Broad inclusion criteria
– Cirrhosis permitted with no platelet cutoff
– Hemoglobin: ≥12 mg/dL (males); ≥11 mg/dL (females)
• Wide range of ART regimens allowed
– Undetectable HIV RNA for >8 weeks on stable ART regimen
• Baseline CD4 count
– ART treated: CD4 T-cell count >200 cells/mm3
– ART untreated: CD4 T-cell count >500 cells/mm3
Sulkowski MS, et al. Abstract #212, AASLD 2013
32
Patients with HCV RNA
<LLOQ (%)
Week 4
100
96
100
EOT
96
SVR12
100
96
98
88
76
80
67
60
40
20
110/114 103/103 87/114
25/26
22/23
23/26
41/41
39/40
28/42
0
Genotype 1
SOF + RBV 24 Weeks
Genotype 2
Genotype 3
SOF + RBV 12 Weeks
Sulkowski MS, et al. Abstract #212, AASLD 2013
33
SOF + RBV
Patients, %
AEs
24 Weeks (n=114)
12 Weeks (n=68)
93
84
36
13
14
16
11
12
11
13
7
3
0
35
21
13
18
9
10
12
10
7
4
1
AEs in ≥10% of patients
Fatigue
Insomnia
Headache
Nausea
Diarrhea
Irritability
URI
Grade 3-4 AEs
Serious AEs
Treatment D/C due to AEs
Death
Sulkowski MS, et al. Abstract #212, AASLD 2013
34
Change in HIV-1 RNA
from Baseline(%)
600
400
200
0
-200
1
2
4
6
8
10
12
Treatment Period (week)
16
20
24
4
12
Follow-up
• Two patients with transient HIV viral breakthrough
– Both with documented nonadherance to ART
• No decrease in CD4 T-cell % with SOF treatment
– Decrease in absolute CD4 T-cell number consistent with ribavirin-mediated decrease in
lymphocyte counts
Sulkowski MS, et al. Abstract #212, AASLD 2013
35
Sofosbuvir and Ribavirin for the Treatment of Established Recurrent
Hepatitis C Infection After Liver Transplantation:
Preliminary Results of a Prospective, Multicenter Study
Michael R. Charlton1, Edward J. Gane2, Michael P. Manns3, Robert S. Brown4, Michael P. Curry5,
Paul Y. Kwo6, Robert J. Fontana7, Richard Gilroy8, Lewis W. Teperman9, Andrew J. Muir10,
John G. McHutchison11, William T. Symonds11, Jill M. Denning11, Lindsay McNair11, Sarah Arterburn11,
Norah Terrault12, Didier Samuel13, Xavier Forns14
1. Mayo Clinic, Rochester, MN, United States.
2. Auckland City Hospital, Auckland, New Zealand.
3. Hannover Medical School, Hannover, Germany.
4. Columbia University, New York, NY, United States.
5. Beth Israel Deaconess Medical Center, Boston, MA, United States.
6. Indiana School of Medicine, Indianapolis, IN, United States.
7. University of Michigan, Ann Arbor, MI, United States.
8. Kansas University Medical Center, Lawrence, KS, United States.
9. NYU Medical Center, New York , NY, United States.
10. Duke University Medical Center, Durham, NC, United States.
11. Gilead Sciences, Foster City, CA, United States.
12. University of California, San Francisco, CA, United States.
13. Université Paris-Sud, Villejuif, France.
14. The Liver Unit, Barcelona, Spain.
36
• Reinfection of the transplanted liver is universal in patients who are
serum HCV RNA-positive at the time of transplantation
• Recurrence of HCV is the most common cause of mortality and graft loss
following transplantation
– 10–50% of patients with recurrent infection progress to cirrhosis within 5 years1
• Once cirrhosis is established, the probability of liver graft failure is 42%
within 12 months2
• Current therapies for HCV treatment used after transplantation have poor
tolerance, poor efficacy, severe adverse reactions, and significant
interactions with immunosuppression medications
1. Berenguer M, et al. Clin Liver Dis 2007;11:355–76; 2. Berenguer M, et al. Hepatology 2002;36:202-10.
Charlton MR, et al. Abstract #LB-2, AASLD 2013
37
Week 0
12
24
36
SOF 400 mg + RBV 400‒1200 mg (N=40)
SVR12
• Patients with recurrent HCV post-liver transplant, all genotypes
• Low, ascending-dose RBV regimen starting at 400 mg/day, escalated
based on hemoglobin levels
• Study objectives
– Primary: sustained virologic response 12 weeks post treatment with
sofosbuvir + RBV in liver transplant recipients
– Secondary: safety, tolerability and viral kinetics
Charlton MR, et al. Abstract #LB-2, AASLD 2013
38
• Inclusion criteria
– Liver transplant ≥6 and ≤150 months prior to enrollment
– Treatment-naïve or experienced
– CPT ≤7 and MELD ≤17
– Primary or secondary, liver alone or liver-kidney transplant
– Absence of organ rejection
• Exclusion criteria
– Current signs of decompensation
– Use of corticosteriods at any dose >5 mg of prednisone/day
Charlton MR, et al. Abstract #LB-2, AASLD 2013
39
Virologic Response
Rate (%)
100
100
100
77
80
60
40
20
40/40
39/39
27/35†
Week 4
EOT*
SVR 4
0
*1 patient still on treatment; †4 patients have not reached SVR4 visit.
Charlton MR, et al. Abstract #LB-2, AASLD 2013
40
100
Patients (%)
80
70
60
35
40
28
25
20
0
5
28/40
14/40
11/40
10/40
2/40
Tacrolimus
Mycophenolate
mofetil
Prednisone
Cyclosporin
Azathioprine
• No interactions reported between SOF and any immunosuppressive agents during study
• 4 patients increased tacrolimus dosing during SOF therapy
Charlton MR, et al. Abstract #LB-2, AASLD 2013
41
n (%)
SOF + RBV
N=40
Overall Grade 3
10 (25)
Overall Grade 4
11 (28)
Lymphocytes (4 G3; 9 G4)
13 (33)
Hemoglobin (G3)
8 (20)
Hyperglycemia (3 G3; 1 G4)
4 (10)
White blood count (G3)
3 (8)
Hyperbilirubinemia (G4)
1 (3)
Lipase (G4)
1 (3)
Neutrophil (G3)
1 (3)
AST (G3)
1 (3)
Charlton MR, et al. Abstract #LB-2, AASLD 2013
42