Interim Results of a Randomized Treatment Study of Emtricitabine/Tenofovir DF (FTC/TDF) and HBIG Withdrawal in Post-Orthotopic Liver Transplant (OLT) Recipients for CHB

[Guest guest]

Interim Results of a Randomized Treatment Study of Emtricitabine/Tenofovir DF

(FTC/TDF) and HBIG Withdrawal in

Post-Orthotopic Liver Transplant (OLT) Recipients for CHB

L Teperman1, J Spivey2, F Poordad3, T Schiano4, N Bzowej5, P 6, D Coombs7,

K Hirsch7, J 7 and F Rousseau7

1The Lea s Organ Transplantation Center, New York University

Medical Center, New York, NY; 2Emory Healthcare, Atlanta, GA; 3Cedars-Sinai

Medical Center, Los Angeles, CA;

4Recanati/ Transplantation Institute, Mount Sinai Hospital, New York, NY;

5California Pacifi c Medical Center, San Francisco, CA; 6Schiff Liver Institute,

University of Miami, School of Medicine, Miami, FL; 7Gilead Sciences

Inc., City, CA

Poster Number

574

Introduction

• HBIG prophylaxis prevents HBV recurrence post-OLT by neutralizing HBsAg and

is the

current standard of care

• Oral antivirals combined with HBIG have reduced the risk of HBV recurrence

to <10%

• Combination treatment with adefovir dipivoxil, lamivudine and HBIG has

successfully

prevented the recurrence of lamivudine resistant HBV post OLT1,2

• However, attempts to either use lamivudine monotherapy or withdraw HBIG from

combination therapy results in high rates of HBV recurrence3,4

• Despite the established effi cacy of HBIG, long-term prophylaxis is

expensive and requires

frequent IV or IM administration

• New potent antivirals such as FTC/TDF may provide a clinical strategy to

reduce or

eliminate the need for HBIG

Primary Objectives

• This ongoing Phase 2 randomized study evaluates the safety and effi cacy of

FTC/TDF with/

without HBIG in preventing recurrence of CHB post OLT

• The aim of this preliminary analysis is to evaluate the effi cacy, safety,

and tolerability of

FTC/TDF in this population

Methods

• Monitor safety laboratory parameters every 8-12 weeks

• Monitor HBV DNA (Roche COBAS TaqMan assay; LLOQ=169 copies/mL) and HBsAg

every 8 to 12 weeks

• Monitor Adverse Events (AEs)

• Resistance surveillance for any patient with HBV DNA ≥ 400 copies/mL

Key Eligibility Criteria

• 18–75 years of age with CHB prior to transplant

• No CHB recurrence after transplant

• Stable patients with ≥ 12 weeks of prophylactic therapy including HBIG

after transplant

• Creatinine clearance ≥ 40 mL/min

• No prior TDF or FTC/TDF treatment after transplant

• HCV, HIV-1, and HDV sero-negative

• No signifi cant renal, cardiovascular, pulmonary, or neurological disease

Results

Virologic Outcomes

• All patients maintained HBV DNA below LLOQ during the study period

─ No evidence of HBV recurrence

─ No re-initiation of HBIG after withdrawal for persistent viremia or

virologic breakthrough

• Subject remained HBsAg negative

• No subject demonstrated evidence of resistance to FTC/TDF

Conclusions

• FTC/TDF is well tolerated in post-OLT patients

• Serum creatinine and creatinine clearance

remained stable on FTC/TDF treatment in post-

OLT patients

• No patient on FTC/TDF who discontinued HBIG

had detectable HBV DNA or HBsAg

References

1. Marzano et al. Liver Transpl 2005

2. Lo et al. Liver Transpl 2005

3. Naoumov et al. J Hepatol 2001

4. Zheng et al. Liver Transpl 2006

[Guest guest]

Interim Results of a Randomized Treatment Study of Emtricitabine/Tenofovir DF

(FTC/TDF) and HBIG Withdrawal in

Post-Orthotopic Liver Transplant (OLT) Recipients for CHB

L Teperman1, J Spivey2, F Poordad3, T Schiano4, N Bzowej5, P 6, D Coombs7,

K Hirsch7, J 7 and F Rousseau7

1The Lea s Organ Transplantation Center, New York University

Medical Center, New York, NY; 2Emory Healthcare, Atlanta, GA; 3Cedars-Sinai

Medical Center, Los Angeles, CA;

4Recanati/ Transplantation Institute, Mount Sinai Hospital, New York, NY;

5California Pacifi c Medical Center, San Francisco, CA; 6Schiff Liver Institute,

University of Miami, School of Medicine, Miami, FL; 7Gilead Sciences

Inc., City, CA

Poster Number

574

Introduction

• HBIG prophylaxis prevents HBV recurrence post-OLT by neutralizing HBsAg and

is the

current standard of care

• Oral antivirals combined with HBIG have reduced the risk of HBV recurrence

to <10%

• Combination treatment with adefovir dipivoxil, lamivudine and HBIG has

successfully

prevented the recurrence of lamivudine resistant HBV post OLT1,2

• However, attempts to either use lamivudine monotherapy or withdraw HBIG from

combination therapy results in high rates of HBV recurrence3,4

• Despite the established effi cacy of HBIG, long-term prophylaxis is

expensive and requires

frequent IV or IM administration

• New potent antivirals such as FTC/TDF may provide a clinical strategy to

reduce or

eliminate the need for HBIG

Primary Objectives

• This ongoing Phase 2 randomized study evaluates the safety and effi cacy of

FTC/TDF with/

without HBIG in preventing recurrence of CHB post OLT

• The aim of this preliminary analysis is to evaluate the effi cacy, safety,

and tolerability of

FTC/TDF in this population

Methods

• Monitor safety laboratory parameters every 8-12 weeks

• Monitor HBV DNA (Roche COBAS TaqMan assay; LLOQ=169 copies/mL) and HBsAg

every 8 to 12 weeks

• Monitor Adverse Events (AEs)

• Resistance surveillance for any patient with HBV DNA ≥ 400 copies/mL

Key Eligibility Criteria

• 18–75 years of age with CHB prior to transplant

• No CHB recurrence after transplant

• Stable patients with ≥ 12 weeks of prophylactic therapy including HBIG

after transplant

• Creatinine clearance ≥ 40 mL/min

• No prior TDF or FTC/TDF treatment after transplant

• HCV, HIV-1, and HDV sero-negative

• No signifi cant renal, cardiovascular, pulmonary, or neurological disease

Results

Virologic Outcomes

• All patients maintained HBV DNA below LLOQ during the study period

─ No evidence of HBV recurrence

─ No re-initiation of HBIG after withdrawal for persistent viremia or

virologic breakthrough

• Subject remained HBsAg negative

• No subject demonstrated evidence of resistance to FTC/TDF

Conclusions

• FTC/TDF is well tolerated in post-OLT patients

• Serum creatinine and creatinine clearance

remained stable on FTC/TDF treatment in post-

OLT patients

• No patient on FTC/TDF who discontinued HBIG

had detectable HBV DNA or HBsAg

References

1. Marzano et al. Liver Transpl 2005

2. Lo et al. Liver Transpl 2005

3. Naoumov et al. J Hepatol 2001

4. Zheng et al. Liver Transpl 2006