Antiviral activity and safety of LB80380 in hepatitis B e antigen–positive chronic hepatitis B patients with lamivudine-resistant disease

✍ Scribed by Man-Fung Yuen; Kwang-Hyub Han; Soon-Ho Um; Seung Kew Yoon; Hye-Ryon Kim; John Kim; Chung Ryeol Kim; Ching-Lung Lai

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 380 KB
• Volume: 51
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.23462

✦ Synopsis

We aimed to determine the antiviral activity and safety of a new nucleotide analogue, LB80380, in chronic hepatitis B (CHB) patients with lamivudine-resistant virus. Sixty-five patients with lamivudine-resistant virus were randomized to receive five ascending daily doses (30, 60, 90, 150, 240 mg) of LB80380. LB80380 was given together with lamivudine for the first 4 weeks, followed by 8 weeks of LB80380 monotherapy. This was then followed by 24 weeks of adefovir. Hepatitis B virus (HBV) DNA levels, serology, liver biochemistry, and safety were monitored. The extent of the HBV DNA reduction at week 12 was dose-dependent. The mean reduction from baseline was 2.81, 3.21, 3.92, 4.16, and 4.00 log 10 copies/mL for the five ascending dose groups. The dose-proportionate effect was statistically significant (P < 0.001) with a decrease of HBV DNA levels by an average of 1.54 log 10 copies/mL for every 1-unit increase in log 10 dose of LB80380. In 93.4% of patients, HBV DNA decreased by >2 log 10 copies/mL, and 11.5% of patients had undetectable HBV DNA levels (<300 copies/mL) by week 12. HBV DNA suppression was maintained during the 24 weeks of adefovir treatment. Hepatitis B e antigen seroconversion and normalization of alanine aminotransferase were seen in 14.6% and 24.6% of patients, respectively, at week 12; 44.6% of patients experienced mild and self-limiting adverse events, none of which were attributed to the study drug. Conclusion: LB80380 at doses of up to 240 mg is safe, well tolerated, and effective at reducing viral load in CHB patients with lamivudine-resistant virus for a period of 12 weeks. (HEPATOLOGY 2010;51:767-776.) T reatment for chronic hepatitis B (CHB) disease is rapidly evolving after the introduction of nucleoside/nucleotide analogs (NAs). The first nucleoside analog lamivudine (L-nucleoside) was li-