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Hepatitis B Update Highlights from AASLD 2012
Efficacy and Safety of Tenofovir DF (TDF) in
Chronic Hepatitis B Virus Infected Patients with
Documented Lamivudine Resistance (LAM-R)
Scott Fung, Peter Kwan, Milotka J. Fabri, Andrzej Horban, Mijomir
Pelemis, Petr Husa, Hie-Won Hann, John F. Flaherty, Benedetta Massetto,
Phillip Dinh, Amoreena C. Corsa, Kathryn M. Kitrinos, John G.
McHutchison, Edward J. Gane
Highlights of AASLD 2012
Hepatitis B
Study ID #20, AASLD 2012
BACKGROUND • Treatment of chronic hepatitis B (HBV) with lamivudine (LAM)
leads to resistance development (LAM-R) in up to 70% of
patients
• Tenofovir DF (TDF) has demonstrated favorable HBV DNA
suppression, safety and tolerability, and no resistance
development through 5 years in treatment-naïve patients.
OBJECTIVE • To evaluate the efficacy and safety of TDF in LAM-R patients in a
in a prospective, randomized trial.
Highlights from AASLD 2012
Efficacy and Safety of Tenofovir DF (TDF) in HBV Infected Patients with
Documented Lamivudine Resistance
Fung, S., et al. ID #20; AASLD 2012
Highlights from AASLD 2012
TDF (N=141) FTC/TDF (N=139) P value
HBV DNA (<400 cp/ml) n (%) 126 (89) 120 (86) 0.43
Normal ALT n (%) 99 (70) 97 (70) 0.94
Normalized ALT a n (%) 49/79 (62) 52/83 (63) 0.93
HBsAg loss b 0 1 (<1)c 0.31
HBeAg loss b 10/65 (15) 9/68 (13) 0.72
HBeAg seroconversion 7/65 (11) 7/68 (10) 0.93
Efficacy and Safety of Tenofovir DF (TDF) in HBV Infected Patients with
Documented Lamivudine Resistance
Fung, S., et al. ID #20; AASLD 2012
RESULTS
a Includes only patients with ALT>ULN at baseline. b HBeAg-positive patients only. c No anti-HBs observed.
Efficacy at Week 96
RESULTS
• Both treatments were well tolerated with 1% (3/280)
discontinuing for an AE (1-TDF, 2-FTC/TDF).
• No patients had a confirmed increase in serum creatinine of
≥ 0.5 mg/dL from BL, 1% (2-TDF) had serum phosphorus
<2 mg/dL, and 3% (5-TDF, 4-FTC/TDF) had CrCL <50 mL/min
(pre-treatment CrCL range for these 9 patients: 49-61 mL/min).
• No clinically relevant bone loss was observed by assessment of
spine and hip bone mineral density monitoring by DEXA and Z
scores; all fractures were trauma-related (5 patients: 3 receiving
TDF, 2 receiving FTC/TDF ).
• No resistance to TDF was detected through 96 weeks.
Highlights from AASLD 2012
Efficacy and Safety of Tenofovir DF (TDF) in HBV Infected Patients with
Documented Lamivudine Resistance
Fung, S., et al. ID #20; AASLD 2012
CONCLUSIONS
• A high rate of HBV DNA suppression with no detectable TDF
resistance was achieved with TDF in patients with documented
LAM-R through 96 weeks.
• Similar efficacy between the mono- and combination therapy
arms supports the use of TDF monotherapy in this population.
• TDF was safe and well tolerated, with a low rate of renal events
and no evidence of clinically relevant bone loss.
Highlights from AASLD 2012
Efficacy and Safety of Tenofovir DF (TDF) in HBV Infected Patients with
Documented Lamivudine Resistance
Fung, S., et al. ID #20; AASLD 2012
Is HBsAg Seroclearance Following
Nucleoside Analogue Therapy Durable in
Patients with Chronic Hepatitis B?
Gi Ae Kim, Young-Suk Lim, Jihyun An, Danbi Lee, Ju Hyun Shim, Kang
Mo Kim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee, Dong Jin Suh
Highlights of AASLD 2012
Hepatitis B
Study ID #313, AASLD 2012
OBJECTIVE
• To evaluate the long term serological and virological
durability of NUC-induced HBsAg seroclearance in
patients with chronic hepatitis B.
METHODS • Retrospective cohort study
• 4578 CHB patients treated with LAM or entecavir; 121 achieved
HBsAg seroclearance; 54 recruited for analysis (LAM, 53;
entecavir, 1).
• Evaluate serological and virological reversion
Highlights from AASLD 2012
Is HBsAg Seroclearance Durable in HBV Patients Following
Nucleoside Analogue Therapy
Kim, G., et al. ID #313
Highlights from AASLD 2012
Is HBsAg Seroclearance Durable in HBV Patients Following
Nucleoside Analogue Therapy
Kim, G., et al. ID #313
Clinical Outcomes after Seroconversion
RESULTS
Characteristic At HBsAg seroclearance
N=54 End of Follow up
N=54 P value
Anti-HBs positive, n (5) 7 (13) 28 (52) <0.001
HBeAg-positive, n (5) 0 0 -
Anti-HBe positive, n (5) 38 (70) 42 (78) 0.289
HBV DNA-positive, n(%) 5 (9) 1 (2) 0.219
ALTa IU/L 16 (12-30) 20 (13-25) 0.564
Cirrhosis, n(%) 14 (26) 12 (22) 0.500
Follow up period, months - 26 (14-43) - a Median (interquartile range).
Highlights from AASLD 2012
Is HBsAg Seroclearance Durable in HBV Patients Following
Nucleoside Analogue Therapy
Kim, G., et al. ID #313
Characteristics OR 95% CI P value
Age 1.008 0.953-1.066 0.777
Gender (Male) 1.345 0.312-5.798 0.691
HBeAg positivity 2.275 0.616-8.396 0.217
Anti-HBe positivity 0.308 0.080-1.189 0.088
HBV DNA level (log10 IU/mL) 1.086 0.859-1.372 0.492
Development of drug-resistant HBV mutations 0.500 0.095-2.628 0.413
Duration of treatment (months) 0.969 0.940-0.999 0.044
Anti-HBsAg seroconversion during follow up after HBsAg seroclearance
0.051 0.006-0.043 0.006
Predictive factors for serological and/or virological conversion
RESULTS
N=54, event (serological and/or virological reversion) number =12.
CONCLUSIONS
• HBsAg seroclearance in CHB patients was durable after
discontinuation of nucleoside analog therapy and was
associated with favorable clinical outcomes.
• Even in patients with lamivudine-resistance HBV
mutations, HBsAg seroclearance in CHB patients was
durable control of HBV infection.
Highlights from AASLD 2012
Is HBsAg Seroclearance Durable in HBV Patients Following
Nucleoside Analogue Therapy
Kim, G., et al. ID #313
Hepatitis B therapy and incidence of
hepatocellular carcinoma in a U.S.
population
Stuart C. Gordon, Lois Lamerato, Loralee B. Rupp, Scott D. Holmberg,
Anne C. Moorman, Philip R. Spradling, Eyasu H. Teshale, Cynthia
Nakasato, Joseph A. Boscarino, Emily Henkle, David R. Nerenz, Nancy
Oja-Tebbe, Mei Lu
Highlights of AASLD 2012
Hepatitis B
Study ID #318, AASLD 2012
PURPOSE • To determine the incidence of hepatocellular carcinoma (HCC)
among treated and untreated chronic hepatitis B (CHB) patients
in four large US health care systems enrolled in the Chronic
Hepatitis Cohort Study (CHeCS).
METHODS • Administrative health care data, supplemented with medical
chart abstraction, were used to identify the time of CHB
diagnosis, start time of antiviral treatment, and time of HCC
diagnosis.
• HCC diagnoses were initially identified via the presence of
ICD9 codes 155.x in administrative data, then confirmed via
chart review and/or tumor registry report.
Highlights from AASLD 2012
Hepatitis B therapy and incidence of hepatocellular carcinoma in a
U.S. population
Gordon, S., et al. ID #318
Highlights from AASLD 2012
Hepatitis B therapy and incidence of hepatocellular carcinoma in a
U.S. population
Gordon, S., et al. ID #318
• 2547 patients in the study population
• 748 of the 2547 received CHB antiviral therapy
• Follow up time after CHB diagnosis was 5 yrs overall
(interquartile range, 3-9 yrs); 6.8 yrs among those receiving
antiviral therapy; 4.9 yrs among those that did not receive
therapy
• During follow up: 71 patients (2.8%) received a diagnosis of
HCC; 19 of 71 (25.4%) received antiviral therapy
• Crude HCC incidence rates: 4.5 cases per 1000 person-yrs
overall; 3.5 cases per 1000 person-yrs for those receiving
antiviral therapy; 5.1 cases per 1000 person-yrs for those not
receiving antiviral therapy
RESULTS
Hepatitis B therapy and incidence of heaptocellular
carcinoma in a U.S. population Gordon, S. et al ID #318
Variable Hazard Ratio (95% CI) P
Antiviral HBV therapy (received vs not received)
0.50 (0.36-0.71)
<.001
Age <.001
40-<50 years vs. 40 years 7.54 (2.07-27.7) .002
50-<60 years vs. 40 years 9.69 (2.73-33.76) <.001
60 years vs. 40 years 23.3 (6.59-81.7) <.001
Charlson/Deyo comorbidity index <.001
Score of 1 vs. 0 1.38 (0.87-2.19) .174
Score 2 or 3 vs. 0 2.15 (1.46-3.16) <.001
Male vs. female 1.94 (1.30-2.87) .001
Final Cox Multivariable Regression Model for Prediction of Hepatocellular Carcinoma
CONCLUSIONS • HBV antiviral therapy was associated with a 50% decrease in
risk of developing HCC in patients with CHB infection
• Other factors associated with increased risk of HCC included
male gender and increasing age>40 at time of CHB diagnosis
Highlights from AASLD 2012
Hepatitis B therapy and incidence of hepatocellular carcinoma in a
U.S. population
Gordon, S., et al. ID #318
Durability after discontinuation of
nucleos(t)ide therapy in hepatitis e antigen
negative chronic hepatitis B patients
Sung Won Cho, Soon Sun Kim, Dami Lee, Jin Hee Cho, Kee Bum Kim, Jae Youn Cheong, Sung won Cho
Highlights of AASLD 2012
Hepatitis B
Study ID #336, AASLD 2012
BACKGROUND • The ideal treatment duration of HBeAg negative hepatitis
patients is not well known. APASL guidelines suggest that if
undetectable HBV-DNA has been documented on three
occasions 6 months apart, discontinuation of treatment can be
considered.
OBJECTIVE • To investigate the frequency of lapse after discontinuation of
nucleos(t)ide (NUC) treatment
• To study factors associated with one year sustained virological
response in chronic HBeAg(-) hepatitis patients
Highlights from AASLD 2012
Durability after discontinuation of nucleos(t)ide therapy in
hepatitis e antigen negative chronic hepatitis B patients
Cho, S.W., et al. ID #336
Durability after discontinuation of nucleos(t)ide therapy in
hepatitis e antigen negative chronic hepatitis B patients
Cho, S.W., et al. ID #336
Virological Relapse Clinical Relapse
6 months after stopping NUC treatment 22 (48.9%) 16 (35.6%)
12 months after stopping NUC treatment 33 (73.3%) 24 (53.3%)
ETV 18/25 (72%) -
LAM 9/14 (64.3%) -
ADV 6/6 (100%) -
Virological and Clinical Relapse Rate After Discontinuation of
NUC Treatment
RESULTS
ETV, entecavir; LAM, lamivudine; ADV, adefovir
Durability after discontinuation of nucleos(t)ide therapy in
hepatitis e antigen negative chronic hepatitis B patients
Cho, S.W., et al. ID #336
Relapse (+) n=33
Relapse (-) n=12
P value
Male, n(%) 23 (69.7) 10 (83.3) 0.466
Mean Age, years (SD) 44.4 (±7.16) 45.4 (±8.12) 0.685
Mean baseline AST, IU/L (SD) 156.45 (±104.9) 159.2 (±85.4) 0.937
Mean baseline ALT, IU/L (SD) 240.3 (±215.7) 235.9 (±124.3) 0.948
Mean HBV DNA, log10 copies/mL (SD) 7.14 (±0.95) 6.9 (±0.74) 0.436
HBV DNA, >108 copies/mL (%) 12 (38.7%) 1 (8.3%) 0.070
Mean duration of treatment, months 36.0 (±6.74) 45.0 (±15.6) 0.077
Liver cirrhosis, n (%) 2 (6.1%) 7 (58.3%) 0.000
Factors Associated with Sustained Virological Response 12 months
After Stopping NUC Treatment
RESULTS
SD, standard deviation; AST, aspartate aminotransferase; ALT, alanine aminotransferase
CONCLUSIONS
• Virological relapse developed in the majority (73.3%) of patients
and clinical relapse developed in approximately half (53.3%) by
12 months after discontinuation of therapy.
• Low baseline HBV DNA levels (<108 copies/ml) and presence
of liver cirrhosis were found to be associated with a low rate of
virological relapse.
Durability after discontinuation of nucleos(t)ide therapy in
hepatitis e antigen negative chronic hepatitis B patients
Cho, S.W., et al. ID #336
Tenofovir monotherapy is effective salvage
therapy of nucleoside-resistant hepatitis B
Jeffrey So, Lay Lay Win, Nitin Sarin, Colina Yim, Hemant Shah,
Jordan J.Feld , E. Jenny Heathcote, David K. Wong
Highlights of AASLD 2012
Hepatitis B
Study ID #364, AASLD 2012
Highlights from AASLD 2012
Tenofovir monotherapy is effective salvage therapy of
nucleoside-resistant hepatitis B
So, J., et al. ID #364
AIM • To assess the effectiveness of tenofovir (TDF) monotherapy in those
with chronic hepatitis B (HBV) infection who have failed treatment with
at least one other nucleos(t)ide reverse transcriptase polymerase
inhibitor (NRTI)
METHODS • Single center, retrospective cohort study
• Identified HBV(+) patients from Nov 1, 2006 to March 31, 2012;
included patients >18 yrs of age with resistance to an NRTI
• Evaluated demographic information, adherence, rate of complete viral
suppression (defined as HBV DNA <60 IU/mL), and viral kinetics and
adverse events of TDF therapy
Highlights from AASLD 2012
Tenofovir monotherapy is effective salvage therapy of
nucleoside-resistant hepatitis B
So, J., et al. ID #364
HBV DNA <60 IU/mL on TDF N=148 (95.5%)
HBV DNA >60 IU/mL at time of initiating TDF (n=155)
HBV DNA still positive on TDF N=7 (4.5%)
Treated with TDF monotherapy (Group 1)
N=58
Treated with TDF and other NRTI (Group 2)
N=90
Switched to TDF monotherapy later
N=58
Still on TDF and other NRTI
N=32
HBV DNA > 60 IU/mL at Time of Initiating Tenofovir (n=155)
Mean HBV DNA at time of initiating TDF, log IU/mL 4.5 (1.8-9.6)
Number achieving HBV DNA <60 IU/mL on TDF 148/155 (95.5%)
Mean time to HBV DNA <60 IU/mL on TDF (months) 5.8 (0.4-39.4)
Number achieving HBV DNA <60 IU/mL within 12 months of starting TDF
134/155 (86.5%)
RESULTS
Tenofovir monotherapy is effective salvage therapy of
nucleoside-resistant hepatitis B
So, J., et al. ID #364
Virologic Response in Group 1 vs. Group 2
Group 1 Group 2 P value
Mean baseline viral load, log IU/mL 4.44 4.65 0.53
Mean duration to HBV DNA <60 IU/mL, months 5.2 6.2 0.34
Highlights from AASLD 2012
Tenofovir monotherapy is effective salvage therapy of
nucleoside-resistant hepatitis B
So, J., et al. ID #364
CONCLUSIONS
• Tenofovir (TDF) is a very effective salvage therapy for those
who fail treatment with other NRTI’s
• Despite concerns raised in the mid-2000’s, TDF treatment
failure due to multidrug resistant HBV strains has not been
observed
• There is no obvious/large advantage for combination therapy
vs. TDF monotherapy
Six Years of Treatment with Tenofovir DF for
Chronic Hepatitis B Virus Infection is Safe and
Well Tolerated and Associated with Sustained
Virological, Biochemical and Serological
Responses with no Detectable Resistance
Patrick Marcellin, Maria Buti, Edward J. Gane, Naoky Tsai, William Sievert,
Ira M. Jacobson, George Germanidis, John F. Flaherty, Phillip Dinh, Kathryn M. Kitrinos, John G. McHutchison, Nezam Afdhal
Highlights of AASLD 2012
Hepatitis B
Study ID #374, AASLD 2012
Highlights from AASLD 2012
Evaluation of 6 Years of Treatment with Tenofovir DF for
Chronic Hepatitis B Infection
Marcellin, P., et al. ID #374
Chronic HBV Patients (HBeAg-
and HBeAg+
TDF 300 mg N=250, 176
Open Label TDF 300 mg QD
ADV 10 mg N=125, 90
Design of Studies 102 (HBeAg-) and 103 (HBeAg+)
Study Year 0 2 1 8 3 4 6 5
Note: Emtricitabine (FTC) could be added for confirmed viremia on/after week 72
Highlights from AASLD 2012
Evaluation of 6 Years of Treatment with Tenofovir DF for
Chronic Hepatitis B Infection
Marcellin, P., et al. ID #374
Response HBeAg- Patients
(study 102) HBeAg+ Patients
(study 103)
Year 5 Year 6 Year 5 Year 6
HBV DNA <400 copies/mL intent-to-treatA
83% 291/350
81% 281/345
65% 160/248
62% 157/251
HBV DNA <400 copies/mL on-treatmentB
99% 292/295
99.6% 283/284
97% 170/175
99% 167/169
Virologic Suppression at Year 6
RESULTS
A LTE-TDF (missing = failure; addition of FTC = failure) B Observed (missing = excluded; addition of FTC = included)
Highlights from AASLD 2012
Evaluation of 6 Years of Treatment with Tenofovir DF for
Chronic Hepatitis B Infection
Marcellin, P., et al. ID #374
TDF-TDF ADF-TDF Total
Adverse events leading to drug discontinuation 9 (2.3%) 2 (1.0%) 11 (1.9%)
Deaths 6 (1.5%) 3 (1.5%) 9 (1.5%)
Serious adverse events 5 (1.3%) 2 (1.0%) 7 (1.2%)
Grade 3 or 4 adverse events 3 (0.8%) 3 (1.5%) 6 (1.0%)
Serum creatinine ≥ 0.5 mg/dL above baseline 5 (1.3%) 4 (2.0%) 9 (1.5%)
Creatinine clearance <50 mL/min 3 (0.8%) 3 (1.5%) 6 (1.0%)
PO4 <2 mg/dL 5 (1.3%) 3 (1.5%) 8 (1.4%)
Summary of Safety During Open-Label Period by Prior
Treatment Assignment
RESULTS
Reasons for discontinuation - Study 102: septic shock (n=1), abdominal pain (n=1), HCC (n=3), dizziness/ fatigue/ attention disturbance (n=1), endometrial cancer (n=1); Study 103: osteoporosis (n=1), blood creatinine increase (n=1), breast cancer (n=1), drug dependence (n=1).
Highlights from AASLD 2012
Evaluation of 6 Years of Treatment with Tenofovir DF for
Chronic Hepatitis B Infection
Marcellin, P., et al. ID #374
CONCLUSIONS
• Virological, biochemical and serological responses were
maintained through 6 years
• HBeAg loss/seroconversion rates of 50% and 37% through 6 yrs
• 11% of patients had confirmed HBsAg loss (8% with seroconversion)
• No resistance to TDF was detected through 6 yrs
• Treatment with TDF was well tolerated
• 80% of 585 patients remained on study at year 6
• <2% of patients discontinued TDF for an adverse event
• Renal events were uncommon (<1.5%) and manageable
• No evidence of bone loss after 2 years of follow up
Incidence and Risk Factors in the
Development of Hepatocellular Carcinoma
(HCC) in Non-Cirrhotic and Cirrhotic Patients
with Chronic Hepatitis B (CHB): Results of a
Multicenter U.S. Cohort Study
Irene S. Sonu, Long H. Nguyen, Christy Chen, Kevin C. Kin, Nghiem B. Ha, Huy
N. Trinh, Aijaz Ahmed, Jiayi Li, Jian Q. Zhang, Mindie H. Nguyen
Highlights of AASLD 2012
Hepatitis B
Study ID #593, AASLD 2012
Highlights from AASLD 2012
Incidence and Risk Factors in the Development of HCC in Non-
Cirrhotic and Cirrhotic Patients with Chronic Hepatitis B (CHB)
Sonu, I. S., et al. ID #593
OBJECTIVE • To determine the incidence of HCC in non-cirrhotic and cirrhotic
patients with chronic hepatitis B and investigate factors related
to higher HCC incidence.
METHODS • Retrospective cohort study involving 3,108 patients with CHB,
including 253 with cirrhosis, seen between 2001 to 2010 at a university
medical center, a community multispecialty medical center, 2
community primary care clinics, and 2 GI clinics in California.
• Patients who had undergone HCC surveillance with imaging studies
and alpha-fetoprotein for at least 12 months were included.
• Patients diagnosed with HCC during the first 6 months of follow up or
co-infected with hepatitis C virus of HIV were excluded.
Highlights from AASLD 2012
Incidence and Risk Factors in the Development of HCC in Non-
Cirrhotic and Cirrhotic Patients with Chronic Hepatitis B (CHB)
Sonu, I. S., et al. ID #593
Overall (n=63) No Cirrhosis (n=25)
Cirrhosis (n=38)
P value
Annual incidence 0.48% (0.38-0.62%) 0.21% (0.14-0.31%) 3.2% (2.4-4.5%) <0.0001
Annual incidence in:
Male (n=1306, 1242, 64)
0.6% (0.5-0.9%)
0.32% (0.2-0.5%)
3.1% (2.2-4.5%)
<0.0001
Female (n=1802, 1613, 189)
0.24% (0.1-0.4%)
0.06% (0.02-0.2%)
3.6% (2.0-6.8%)
Annual HCC Incidence in CHB Patients With and Without Cirrhosis
RESULTS
Highlights from AASLD 2012
Incidence and Risk Factors in the Development of HCC in Non-
Cirrhotic and Cirrhotic Patients with Chronic Hepatitis B (CHB)
Sonu, I. S., et al. ID #593
Adjusted Hazard Ratio P value
Age 1.05 (1.03-1.08) <0.0001
Sex Female (reference)
Male
2.55 (1.31-4.97)
0.006
Chronic hepatitis B Without Cirrhosis (reference)
With Cirrhosis
3.10 (2.36-4.07)
<0.001
Ethnicity Non-Asian (reference)
Asian
2.39 (0.58-9.87)
0.23
Predictors for HCC Using a Cox Proportional Hazards Model
Highlights from AASLD 2012
Incidence and Risk Factors in the Development of HCC in Non-
Cirrhotic and Cirrhotic Patients with Chronic Hepatitis B (CHB)
Sonu, I. S., et al. ID #593
CONCLUSIONS
• Across all patients with CHB recruited from both community and
academic centers, HCC incidence is higher in males and
increases with increasing age.
• In patients without cirrhosis, annual HCC incidence ranged from
0.8% in young males to close to 1.0% in males older than 50,
while it remained near 0.1% in females older than 50.
• Among those with cirrhosis, annual incidence of HCC is similarly
high in males and females and
Peginterferon Lambda, a New Potential
Therapeutic Option for the Treatment of Chronic
Hepatitis B: A Phase 2B Comparison with
Peginterferon Alfa in Patients with
HBeAg-Positive Disease
Henry Lik-Yuen Chan, Sang Hoon Ahn, Ting-Tsung Chang, Cheng-Yuan Peng, David
K. Wong, Carla S. Coffin, Seng Gee Lim, Pei-Jer Chen, Harry L. Janssen, Patrick
Marcellin, Lawrence Serfaty, Stefan Zeuzem, Wenhua Hu, Linda Critelli, Juan Carlos
Lopez-Talavera, Elizabeth L. Cooney
Highlights of AASLD 2012
Hepatitis B
Study ID #LB-14, AASLD 2012
Highlights from AASLD 2012
Peginterferon Lambda, a New Potential Therapeutic Option for
the Treatment of Chronic Hepatitis B: A Phase 2B Comparison
Chan, H. L., et al. ID #LB-14
BACKGROUND
• Peginterferon lambda-1a (Lambda) is the pegylated form of interferon
lambda-1a, a type 3 interferon with demonstrated activity against the
hepatitis B virus (HBV) in vitro and in transgenic mice
• Lambda is currently in phase III development for chronic hepatitis C
virus (HCV), where Lambda has shown greater early virologic effect
and improved tolerability compared to alpha-interferon
• A phase 2b study of Lambda vs. pegylated interferon alpha-2a for
chronic hepatitis B (CHB) has been initiated (LIRA-B study); this
reports the week 24 interim results
Highlights from AASLD 2012
Peginterferon Lambda, a New Potential Therapeutic Option for
the Treatment of Chronic Hepatitis B: A Phase 2B Comparison
Chan, H. L., et al. ID #LB-14
Mean value for HBV DNA at baseline: 7.8 log10 IU/mL
Serum HBV DNA Change From Baseline
Lambda Alfa
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.5
-4.00 4 8 12 16 20 24
HB
V D
NA
me
an lo
g10
ch
an
ge
fro
m b
ase
line
± S
E (
IU/m
L)
Weeks
80
83
77
78
78
81
32
35
75
75
74
74
75 = N
72 = N
P= <0.0001 0.0018 0.0272 0.1203
-1.78
-2.58
-2.28
-2.77
Highlights from AASLD 2012
Peginterferon Lambda, a New Potential Therapeutic Option for
the Treatment of Chronic Hepatitis B: A Phase 2B Comparison
Chan, H. L., et al. ID #LB-14
Mean value for qHBsAg at baseline: 4.0 log10 IU/mL
Serum qHBsAg Change From Baseline
Lambda Alfa
0.0
-0.1
-0.2
-0.3
-0.4
-0.5
-0.6
-0.7
-0.8
-0.9
-1.00 4 8 12 16 20 24
qH
Bs
Ag
a
mea
n log
10
ch
an
ge
fro
m b
ase
line
± S
E
Weeks
77
83
75
76
75 = N
73= N
P= <0.0002 0.0075
-0.27
-0.67
-0.39
-0.65
Highlights from AASLD 2012
Peginterferon Lambda, a New Potential Therapeutic Option for
the Treatment of Chronic Hepatitis B: A Phase 2B Comparison
Chan, H. L., et al. ID #LB-14
Patients, n (%) Lambda (180 µg)
N=80 Alpha (80 µg)
N=83
Any AE 72 (90) 75 (90)
Serious AE 4 (5) 6 (7)
Aes leading to discontinuation of therapy 4 (5) 7 (8)
Dose Reductions due to AEc Neutropenia Thrombocytopenia ALT increase
6 (8) 0 0
4 (5)
21 (25) 12 (15)
1 (1) 2 (2)
ALT Flares >2xbaseline and >10x ULNb >2xbaseline and >5xULNc
12 (15) 27 (34)
6 (7)
13 (16)
A Selected events of interest shown. B NIH adopted criteria for ALT flare. C Minimum-accepted criteria for ALT flare per literature.
Safety and Adverse Events
Highlights from AASLD 2012
Peginterferon Lambda, a New Potential Therapeutic Option for
the Treatment of Chronic Hepatitis B: A Phase 2B Comparison
Chan, H. L., et al. ID #LB-14
CONCLUSIONS
• Lambda demonstrated greater early efficacy than alfa, as
defined by HBV DNA and qHBsAg change from baseline at
weeks 12 and 24; HBeAg responses were comparable through
week 24.
• There were fewer hematologic abnormalities and flu-like or
musculoskeletal symptoms with Lambda vs alfa.
• These interim study results are consistent with findings from
Lambda studies in HCV and support ongoing study of Lambda
in CHB.