Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection

Sang Hoon Ahn, Won Kim, Young Kul Jung, Jin Mo Yang, Jae Young Jang, Yong Oh Kweon, Yong Kyun Cho, Yoon Jun Kim, Gun Young Hong, Dong Joon Kim, Soon-Ho Um, Joo Hyun Sohn, Jin Woo Lee, Sung Jae Park, Byung Seok Lee, Ju Hyun Kim, Hong Soo Kim, Seung Kew Yoon, Moon Young Kim, Hyung Joon YimKwan Sik Lee, Young Suk Lim, Wan Sik Lee, Neung Hwa Park, So Young Jin, Kyun Hwan Kim, Won Choi, Kwang Hyub Han

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Abstract

Background & Aims: Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea. Methods: We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks. Results: After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV–BSV and 85.7% of patients in the TDF–BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups. Conclusions: BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.

Original languageEnglish
Pages (from-to)1850-1859.e4
JournalClinical Gastroenterology and Hepatology
Volume17
Issue number9
DOIs
Publication statusPublished - 2019 Aug 1

Keywords

  • Acyclic Nucleotide Phosphonate
  • Drug Resistance
  • eGFR
  • Nephrotoxicity

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Ahn, S. H., Kim, W., Jung, Y. K., Yang, J. M., Jang, J. Y., Kweon, Y. O., Cho, Y. K., Kim, Y. J., Hong, G. Y., Kim, D. J., Um, S-H., Sohn, J. H., Lee, J. W., Park, S. J., Lee, B. S., Kim, J. H., Kim, H. S., Yoon, S. K., Kim, M. Y., ... Han, K. H. (2019). Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection. Clinical Gastroenterology and Hepatology, 17(9), 1850-1859.e4. https://doi.org/10.1016/j.cgh.2018.11.001