Clin Mol Hepatol.  2021 Apr;27(2):346-359. 10.3350/cmh.2020.0307.

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial

Affiliations
  • 1Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
  • 2Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
  • 3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  • 4Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
  • 5Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, Korea
  • 6Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Korea
  • 7Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 8Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 9Department of Internal Medicine, Kwangju Christian Hospital, Gwangju, Korea
  • 10Department of Internal Medicine and Center for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
  • 11Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
  • 12Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
  • 13Department of Internal Medicine, Paik Hospital, Inje University, Busan, Korea
  • 14Department of Gastroenterology and Hepatology, Chungnam National University School of Medicine, Daejeon, Korea
  • 15Department of Internal Medicine, Gacheon University College of Medicine, Incheon, Korea
  • 16Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
  • 17Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
  • 18Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
  • 19Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 20Department of Internal Medicine, Chonnam University Medical School, Gwangju, Korea
  • 21Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, Korea

Abstract

Background/Aims
Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients.
Methods
Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV).
Results
Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group.
Conclusions
BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Keyword

Besifovir; Hepatitis B; Chronic; Drug resistance; Bone mineral density; Nephrotoxicity
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