Do Seon Song1, Won Kim2, Sang Hoon Ahn3, Hyung Joon Yim4, Jae Young Jang5, Young Oh Kweon6, Yong Kyun Cho7, Yoon Jun Kim8, Gun Young Hong9, Dong Joon Kim10, Young Kul Jung4, Joo Hyun Sohn11, Jin-Woo Lee12, Sung Jae Park13, Byung Seok Lee14, Ju Hyun Kim15, Hong Soo Kim16, Seung Kew Yoon17, Moon Young Kim18, Kwan Sik Lee3, Young Suk Lim19, Wan Sik Lee20, Jin Mo Yang1, Kyun-Hwan Kim21, Kwang-Hyub Han3, Soon Ho Um4. 1. Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, Korea. 2. Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. 3. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. 4. Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. 5. Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, Korea. 6. Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Korea. 7. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. 8. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. 9. Department of Internal Medicine, Kwangju Christian Hospital, Gwangju, Korea. 10. Department of Internal Medicine and Center for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea. 11. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. 12. Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. 13. Department of Internal Medicine, Paik Hospital, Inje University, Busan, Korea. 14. Department of Gastroenterology and Hepatology, Chungnam National University School of Medicine, Daejeon, Korea. 15. Department of Internal Medicine, Gacheon University College of Medicine, Incheon, Korea. 16. Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea. 17. Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. 18. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. 19. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 20. Department of Internal Medicine, Chonnam University Medical School, Gwangju, Korea. 21. Department 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. CONCLUSION: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).
RCT Entities:
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 Bpatients. 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. CONCLUSION: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).
Entities:
Keywords:
Besifovir; Bone mineral density; Drug resistance; Hepatitis B, Chronic; Nephrotoxicity
Authors: Jong Chul Kim; Hye Young Lee; Ah Ram Lee; Mehrangiz Dezhbord; Da Rae Lee; Seong Ho Kim; Juhee Won; Soree Park; Na Yeon Kim; Jae Jin Shin; Sang Gyune Kim; Young Seok Kim; Jeong-Ju Yoo; Kyun-Hwan Kim Journal: Biomedicines Date: 2022-01-26