SAFETY AND EFFICACY OF SWITCHING TO BESIFOVIR DIPIVOXIL MALEATE IN VIROLOGICALLY SUPPRESSED CHRONIC HEPATITIS B PATIENTS WITH TENOFOVIR DISOPROXIL FUMARATE: A RANDOMIZED CONTROLLED TRIAL

Abstract

Background: Besifovir dipivoxil maleate (BSV), a nucleotide analogue with potent antiviral activity against hepatitis B virus (HBV), showed comparable antiviral activity to tenofovir disoproxil fumarate (TDF) and a better safety profile in the phase 3 trial. Previously reported 24-week interim results showed that chronic hepatitis B (CHB) patients who switched to BSV from TDF maintained viral suppression and improved bone and renal safety. Herein, we report 48-week data of the phase 4 trial. Methods: In this randomized, multicenter, parallel, open-label, non-inferiority trial, a total of 153 patients treated with TDF for 48 weeks or more and who had HBV DNA <20 IU/mL at screening were randomized to receive BSV 150 mg or TDF 300 mg for 48 weeks. The primary efficacy analysis was the proportion of patients with HBV DNA level < 20 IU/mL at week 48. Efficacy analyses included virologic, biochemical, and serologic responses, and safety assessments included changes in bone mineral density (BMD) and renal outcomes. Results: A total of 130 patients were included for the Per protocol analysis (BSV group=64, TDF group=66). The baseline characteristics of patients in both groups were not statistically significant. After 48 weeks of treatment, 100.0% of patients who received BSV and 98.5% of patients who received TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF (95% CI -0.01 to 0.04; p = 1.000). Only one HBsAg seroconversion has occurred in the BSV group; in HBeAg positive subjects, 14.8% (4/27) and 10.7% (3/28) achieved HBeAg loss in the BSV and the TDF groups, respectively. 90.6% and 86.4% of patients showed serum alanine aminotransferase normalization in the BSV and the TDF groups, respectively. Overall, adverse events (AEs) were similar, but serious AEs occurred in 1 case of the BSV group while in 6 cases of the TDF group. All bone turnover biomarkers were statistically significantly improved in the BSV group compared to the TDF group; similarly, hip and spine BMD increased in the BSV group. The mean % changes of estimated glomerular filtration rates tended better in the BSV group (1.67±11.73%) than those in the TDF group (-1.24±11.02%) without statistical significance. Conclusion: In virologically suppressed CHB patients who switched to BSV from TDF, the BSV group demonstrated non-inferior antiviral efficacy compared to the TDF group and improved safety.