icon-folder.gif   Conference Reports for NATAP  
 
  40th Annual Meeting of the
European Association
for the Study of the Liver
April 13-17, 2005
Paris, France

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Adefovir Week 144 Efficacy in HBeAg+
 
 
 

Reported by Jules Levin

"Increasing Serologic, Virologic and Biochemical Response Over Time to Adefovir (ADV) 10 mg in HBeAg+ Chronic Hepatitis (CHB) Patients"

P Marcellin1, TT Chang2, SG Lim3, W Sievert4, M Tong5, S Arterburn6, S Xiong6, CL Brosgart6, and G Currie6 for the 437 Study Group1Hopital Beaujon, Clichy, France; 2National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China; 3National University Hospital, Singapore; 4Monash Medical Centre, Victoria, Australia; 5Huntington Medical Center Research Institute, Huntington, California, USA;6Gilead Sciences, Inc., Foster City, California, USA

Marcellin reported this data and information at the EASL meeting, April 13-17, Paris, 2005.
 
Investigator summary:
The proportion of patients with clinical benefit increased over time:
--Undetectable HBV DNA increased (48% week 144)
--ALT normalization increased (80% week 144)
--HBeAg loss and seroconversion increased (53% & 46% week 144)
 
Safety profile over 144 weeks consistent with first 48 weeks:
--safety profile similar to placebo at 48 weeks
 
Resistance to adefovir is delayed and infrequent in this study population.
 
INTRODUCTION
Nucleotide analogue of adenosine monophosphate
Activity against wild-type and lamivudine-resistant (LAM-R) HBV1-5
10 mg once daily orally
Durable HBV DNA suppression with a high threshold for the development of resistance
Safety profile similar to placebo in 48 week controlled trials
 
KEY INCLUSION CRITERIA
HBeAg+ , anti-HBe- and HBsAg+
Compensated liver disease
HBV DNA ³ 106 copies/mL
ALT x ULN ³ 1.2 —10
Adequate renal function
 

STUDY DESIGN*

*misallocation: patients received significant periods of intermittent dosing in Yr 2.

HBV DNA UNDETECTABLE & ALT NORMALIZED

Kaplan-Meier Estimates

HBeAg LOSS & SEROCONVERSION OVER TIME

Kaplan-Meier Estimates

DURABILITY of HBeAg SEROCONVERSION OFF THERAPY

Median duration off ADV therapy: 55 weeks (range 5-114)

No patient who discontinued treatment with adefovir had a serum creatinine elevation >0.5 mg/dL above baseline or a serum phosphorous <2.0 mg/dL.

No patient had an ALT elevation accompanied by signs of worsening liver function.

RESISTANCE EVALUATION

All samples with detectable serum HBV DNA by PCR (>1000 copies/ml) at weeks 48 & 144* were analyzed.

--Incidence of ADV resistance at week 144* (3%, 2/65)