best of hcv from aasld 2013

1

Best of HCVFrom AASLD 2013

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.

Darrell Crawford, MDBrisbane, Australia

2

Abstract #LB-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.

3

• 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

Direct-Acting Antiviral Agents

Everson GT, et al. Abstract #LB-1, AASLD 2013

4

Randomized, Phase 2b Open-Label Study (AI443-014)

• 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


DCV 30 mg BID + ASV 200 mg BID + BMS-791325 75 mg BID

DCV 30 mg BID + ASV 200 mg BID + BMS-791325 150 mg BID

12-week follow-upAdditional

follow-up to SVR48

0 12 24

N = 80

N = 86

Week

Primary endpoint: SVR12

5

Efficacy Through SVR12 (Observed)

Series10

20

40

60

80

100

End of Treatment SVR4 SVR12

Res

pons

e, %

of p

atie

nts

DCV + ASV + ‘325 75 mg

DCV + ASV + ‘325 150 mg

97.5 94.2 92.4 91.7 92.2 91.7

78/80 81/86 73/79 77/84 71/77 77/84


6

Event, n (%)

DCV + ASV + ‘325 75 mg

N = 80

DCV + ASV + ‘325 150 mg

N = 86Total

N = 166Serious AEs 1 (1.3) 2 (2.3) 3 (1.6)AEs leading to discontinuation 1 (1.3) 1 (1.2) 2 (1.1)Grade 3/4 AEs 0 1 (1.2) 1 (0.5)Most frequent on-treatment AEs (≥ 10%)

Headache 17 (21.3) 24 (27.9) 41 (24.7)Diarrhea 12 (15.0) 13 (15.1) 25 (15.1)Fatigue 12 (15.0) 7 (8.1) 19 (11.4)Nausea 10 (12.5) 7 (8.1) 17 (10.2)

Grade 3/4 lab abnormalitiesAspartate aminotransferase (AST) 1 (1.3) 0 1 (0.5)Glucose, fasting serum (high) 1 (1.3) 1 (1.2) 2 (1.2)Phosphorus, inorganic 0 1 (1.2) 1 (0.5)Bilirubin, total 0 1 (1.2) 1 (0.5)

Safety Outcomes


7

Abstract #211

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.

8

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)

Virologic Response

aIneligible naïve: n=100; Intolerant: n=35 bNull responders: n=48; Partial responders: n=36; Undetermined: n=3

Chayama K, et al. Abstract #211, AASLD 2013

9

Abstract #73

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.

10

Direct Acting Antiviral Agents

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

Sofosbuvir/Ledipasvir FDC• Once daily, oral fixed-dose (400/90 mg)

combination tablet• No food effect• >2000 patients treated

SOFNucleotidePolymeraseinhibitor

LDVNS5Ainhibitor

Gane EJ, et al. Abstract #73, AASLD 2013

11

Study Design

• Primary endpoint: SVR12 (HCV RNA <LLOQ)• Patients enrolled in ELECTRON or ELECTRON 2 (GT1, F3/F4)• All groups were open label

GT 1 Experienced

GT 1 Naïve

Wk 0 Wk 6 Wk 12

F4

F3/F4

F0/F1/F2

SOF/LDV FDC (n=10)

SOF/LDV FDC + GS-9669 (n=25)

SOF/LDV FDC + RBV (n=10)



Ran

dom

ized

Ran

dom

ized SVR12


12

SVR 12 Results: GT 1 Treatment-Experienced Patients with Advanced Fibrosis/Cirrhosis

SOF/LDV SOF/LDV + RBV0

102030405060708090

100

70

100

SV

R 1

2 (

%)

SOF/LDV + RBV SOF/LDV + GS9669

100 100

Duration (wk) 12 12

F4 only F3/F4

12 12

7/10 9/9 25/25* 26/26*

*From ELECTRON 2Gane EJ, et al. Abstract #73, AASLD 2013

13

SVR12 Results: Treatment DurationGenotype 1, Treatment-naïve, No Cirrhosis

SOF + LDV + RBV* SOF/LDV + RBV SOF/LDV + RBV0

102030405060708090

100100 100

68

SV

R 1

2 (

%)

Duration (wk) 12 8 6

25/25 21/21 17/25

†

*Gane et al. EASL 2013. †Lawitz et al, Abstract #215, AASLD 2013 (LONESTAR)


14

Conclusions

• 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


15

Abstract #75

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.

16

Background and Aims

• 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

17

PEARL-I Study Design

Substudy 1:PatientsWithoutCirrhosis

Substudy 2:Patients With Compensated Cirrhosis

Group 1 40

Group 2 40

Group 3 40

Group 4 40

Group 5 40

Group 6 40

Group 7 40

Group 8 40

PlannedN

HCV Genotype/RegimenTreatment Experience Week 12 Week 24

GT4 ABT-450/r + ABT-267Treatment-naïve

GT1b ABT-450/r + ABT-267Treatment-naïve

GT1b ABT-450/r + ABT-267Null Responders

GT4 ABT-450/r + ABT-267 + rbvTreatment-naïve

GT4 ABT-450/r + ABT-267Partial/Null Responders & Relapsers

GT4 ABT-450/r + ABT-267 + rbvPartial/Null Responders & Relapsers

GT1b ABT-450/r + ABT-267Treatment-naïveGT1b ABT-450/r + ABT-267Partial/Null Responders & Relapsers

BL


18

Efficacy: Treatment-Naïve Patients, ITT

Week 4 Week 12 (EOTR)

SVR4 SVR12

0

20

40

60

80

100P

erc

en

tag

e o

f Pa

tien

ts (

%) 100 97.6

42/42 41/42 41/42 40/42

97.6 95.2


19

39/40 39/40 37/40

97.597.5 92.5 90.0

36/40

Efficacy: Prior Null Responders, ITT

Week 4 Week 12(EOTR)

SVR4 SVR12

0

20

40

60

80

100P

erc

en

tag

e o

f Pa

tien

ts (

%)


20

Treatment-Emergent Adverse Events (AEs) Occurring in >10% of Patients in Either Group

Event, n (%)GT1b-infected

Treatment-naïve Patients(N=42)

GT1b-infectedPrior 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


21

Abstract #LB-4

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.

22

Study Design

SOF + PEG/RBV SVR12GT 2/3(N=47)

• 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

Wk 0 Wk 12 Wk 24 Wk 36

Lawitz E, et al. Abstract #LB-4, AASLD 2013

23

Series10

20

40

60

80

100 89 9683

Results: SVR12 by HCV Genotype

Overall GT 2 GT 3

42/47 22/23 20/24

SV

R1

2 (%

)


24

Results: SVR12 by Cirrhosis Status

GT 2 GT 30

20

40

60

80

100100 8393 83

No Cirrhosis CirrhosisS

VR

12

(%)

9/9 13/14 10/12 10/12

Error bars represent 95% confidence intervals.


25

Results: Adverse Events

Patients, n (%)

SOF + PEG/RBV12 weeks

(N=47)

Overall safety

AEs 45 (96)

Grade 3-4 AEs 15 (32)

Serious AEs 4 (9)

Treatment discontinuation due to AEs 2 (4)

Hematologic abnormalities

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)


26

Conclusions

• 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


27

Abstract #1085

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.

28

Wk 0 Wk 24 SVR4, SVR12, SVR24

Placebo*(n = 85)

Sofosbuvir + Ribavirin (n = 250)

Sofosbuvir + Ribavirin(n = 84)*

*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.

VALENCE: Study Design

Wk 12

Zeuzem S, et al. Abstract #1085, AASLD 2013

29

0

20

40

60

80

100 97 10091 88

SVR12 in GT 2 Patients Treated for 12 Weeks

SV

R1

2 (

%)

*3 of 11 patients (27%) with HCV GT 3 who received 12 weeks of SOF+RBV achieved SVR 12.


0

20

40

60

80

100 9385

SVR12 in GT 2 and 3 Patients*

SV

R1

2 (

%)

GT 2SOF+RBV 12 wk

GT 3SOF+RBV 24 wk

Naïve,Noncirrhotic

Naïve,Cirrhotic

Experienced,Noncirrhotic

Experienced,Cirrhotic

68/73212/250 29/30 2/2 30/33 7/8

30

SVR12 in GT 3 Patients Treated for 24 Weeks

0

20

40

60

80

100 94 92

87

60

SV

R1

2 (

%)

Naïve,Noncirrhotic

Naïve,Cirrhotic

Experienced,Noncirrhotic

Experienced,Cirrhotic

86/92 12/13 27/4587/100


31

Abstract #212

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.

32

36

Wk 0 Wk 12 Wk 24 Wk 36

SOF + RBV, n=114 GT 1 TN SVR12

SOF + RBV, n=41GT 2/3 TE SVR12

SOF + RBV, n=68 GT 2/3 TN SVR12

Study Design

• 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

33

Results: Virologic ResponseP

atie

nts

wit

h H

CV

RN

A

<L

LO

Q (

%)

Genotype 1 Genotype 2 Genotype 30

20

40

60

80

100 96 96 100100 96 98

76

88

67

87/114 23/26 28/42110/114 103/103 22/2325/26 39/4041/41

SOF + RBV 24 Weeks SOF + RBV 12 Weeks

Week 4 EOT SVR12


34

Results: Safety Summary

Patients, %

SOF + RBV

24 Weeks (n=114) 12 Weeks (n=68)

AEs 93 84AEs in ≥10% of patients

Fatigue 36 35Insomnia 13 21Headache 14 13Nausea 16 18Diarrhea 11 9Irritability 12 10URI 11 12

Grade 3-4 AEs 13 10Serious AEs 7 7Treatment D/C due to AEs 3 4Death 0 1


35

HIV Safety

-200

0

200

400

600C

han

ge

in

HIV

-1 R

NA

fr

om

Bas

elin

e(%

)

1 2 4 6 8 10 12 16 20 24 4 12Treatment Period (week) 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 countsSulkowski MS, et al. Abstract #212, AASLD 2013

36

Abstract #LB-2

Sofosbuvir and Ribavirin for the Treatment of Established Recurrent Hepatitis C Infection After Liver Transplantation:

Preliminary Results of a Prospective, Multicenter Study

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.

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

37

Background

• 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 medications1. 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

38

Study Design and Objectives

• 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

SOF 400 mg + RBV 400‒1200 mg (N=40) SVR12

Week 0 12 24 36


39

Key Inclusion/Exclusion Criteria• 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


40

Results: Virologic Response

Week 4 EOT* SVR 40

20

40

60

80

100100 100

77

39/3940/40 27/35†Viro

logi

c R

espo

nse

Rat

e (%

)

*1 patient still on treatment; †4 patients have not reached SVR4 visit.


41

Concomitant Immunosuppression

• No interactions reported between SOF and any immunosuppressive agents during study

• 4 patients increased tacrolimus dosing during SOF therapy

0

20

40

60

80

100

70

3528 25

511/4028/40 14/40 10/40 2/40

Tacrolimus Mycophenolate mofetil

Prednisone Cyclosporin Azathioprine

Pat

ient

s (%

)


42

Results: Grade 3 and 4 Laboratory Abnormalities

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)


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