The 36th Annual Meeting of EASL
April 18-22, 2001
Prague, Czech Republic
Entecavir: new Hepatitis B drug in early research
A PHASE II STUDY OF ENTECAVIR
VS LAMIVUDINE IN ADULTS WITH CHRONIC HEPATITIS B
C. Lai, M. Rosmawati, J. Lao, H. Van Vlierberghe, F. Anderson, N. Thomas, D. De Hertogh Department of Medicine, Queen Mary Hospital., University Hospital, Malaysia., Cebu Doctors Hospital, Philippines., University Hospital, Belgium., Vancouver Hospital, Canada., Bristol-Myers Squibb, USA., Bristol-Myers Squibb, USA
Entecavir (ETV) is a guanosine nucleoside analogue which has demonstrated potent activity against hepatitis B virus (HBV) in vitro (ED50=4nM), in animal models and in a previous 4-week dosing trial in adults with chronic hepatitis B.
The safety and antiviral activity of 3 doses of ETV (0.01, 0.1 and 0.5 mg QD) given for 24 weeks compared to lamivudine (LVD) 100 mg QD were studied in a double-blind, randomized trial in 180 subjects (45/arm). HBeAg-positive and -negative subjects with HBV DNA levels >40 MEq/mL by the Quantiplex bDNA assay who had not received >12 weeks of prior anti-HBV therapy with nucleosides were eligible. The primary endpoint was mean log10 HBV DNA measured by the Roche Amplicor PCR assay at Week 22.
177 subjects started study drug and 169 were evaluable for efficacy. The majority were male (74%), Asian (57%), HBeAg-positive (81%), with mean ALT of 109 IU/L and mean log10 HBV DNA of 2.8 MEq/mL. 22% of subjects had received prior interferon therapy. All 3 doses of ETV were active, but the 0.01 mg dose was less effective than the 0.1 and 0.5 mg doses. ETV 0.1 and 0.5 mg doses were both superior to LVD with mean log10 reductions in HBV DNA by PCR of 4.3, 4.7 and 3.4, respectively (p=0.0001) at Week 22. Only 6 subjects (4 ETV, 2 LVD) lost HBeAg. There was a suggestion of greater normalization of serum ALT for the 2 higher doses of ETV (83% and 66%) than for LVD (59%), but these differences were not statistically significant. ETV was generally well tolerated. Mild-to-moderate adverse events attributable to the nervous system were more frequent in the ETV 0.5 mg group than for LVD; however, only 1 ETV subject in the 0.1 mg group discontinued after 18 weeks of dosing due to lethargy and photosensitivity.
Entecavir at doses of 0.1 and 0.5 mg once daily has superior antiviral activity to lamivudine and is well tolerated.
Phase III Entecavir studies will begin sonn in HBV-infected, and in HBV/HIV coinfected initial study should begin later this year. Ongoing studies will report later this year on Entecavir effectiveness against 3TC resistant virus.