| Entecavir Is Superior to Lamivudine at Reducing HBV DNA Regardless of Baseline ALT Levels
Currently in phase III clinical development, entecavir (ETV) is an investigational oral nucleoside analogue discovered at Bristol-Myers Squibb (BMS). Entecavir is a potent and selective inhibitor of hepatitis B virus (HBV) polymerase.
BMS recently submitted a new drug application (NDA) for entecavir to the U.S. Food and Drug Administration (FDA) and a marketing authorization application (MAA) for entecavir with the European Medicines Evaluation Agency (EMEA). The applications include data from three extensive Phase III clinical trials investigating more than 1,600 patients on five continents.
Chronic hepatitis B patients with low serum alanine aminotransferase (ALT) levels typically show reduced or absent responses to interferon and lamivudine (LVD).
Data from a Phase II dose-ranging trial in nucleoside-naive patients suggested that this is not the case for ETV. This analysis assesses the influence of baseline ALT levels on the clinical efficacy of ETV 0.5 mg QD compared to LVD 100 mg QD in a Phase III trial in 709 nucleoside-naive patients with chronic hepatitis B (ETV-022).
Patients were HBeAg (+) with baseline HBV DNA ≥ 3 MEq/ml by bDNA assay and ALT ≥ 1.3 x ULN. Efficacy endpoints included proportions of patients with HBV DNA < 0.7 MEq/ml by bDNA, proportions with HBV DNA < 400 copies/mL by PCR, and HBV DNA reduction by PCR. Efficacy results for both treatment groups were analyzed within subgroups with baseline ALT < 2.6 x ULN or ≥ 2.6 x ULN.
Results
Baseline disease characteristics were comparable in the ETV and LVD groups. Mean baseline viral loads were ETV: 9.61 log10 c/mL; LVD: 9.69 log10 c/mL. The baseline ALT < 2.6 x ULN and ≥ 2.6 x ULN subgroups comprised 186 and 168 ETV patients, respectively, and 190 and 164 LVD patients, respectively.
Virologic efficacy results at week 48 by treatment and baseline ALT subgroup are shown in the table. ETV was highly effective at reducing HBV DNA regardless of baseline ALT level, and was superior to LVD by all virologic assessments.
In contrast, among LVD-treated patients, HBV DNA reduction and the proportion of patients with undetectable HBV DNA levels by bDNA or PCR assays was attenuated in the lower baseline ALT subgroup.
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Conclusions
These data confirm Phase II observations showing that in patients with chronic hepatitis B, entecavir 0.5 mg is highly effective and is superior to LVD at reducing HBV DNA regardless of baseline ALT levels.
11/01/04
Reference
M Rosmawati and others (the BEHOLD Study Group). ENTECAVIR IS SUPERIOR TO LAMIVUDINE AT REDUCING HBV DNA IN PATIENTS WITH CHRONIC HEPATITIS B REGARDLESS OF BASELINE ALANINE AMINOTRANSFERASE LEVELS. Abstract 1136 (poster). 55th AASLD. October 29-November 2, 2004. Boston, MA.
[此贴子已经被作者于2004-11-4 10:32:10编辑过] | 
发表于 2004-11-5 00:24
