Am J Gastroenterol. 2020 May 1. doi: 10.14309/ajg.0000000000000605. [Epub ahead of print]
Besifovir Dipivoxil Maleate 144-Week Treatment of Chronic Hepatitis B: An Open-Label Extensional Study of a Phase 3 Trial.
Yim HJ1, Kim W2, Ahn SH3, Yang JM4, Jang JY5, Kweon YO6, Cho YK7, Kim YJ8, Hong GY9, Kim DJ10, Jung YK1, Um SH1, Sohn JH11, Lee JW12, Park SJ13, Lee BS14, Kim JH15, Kim HS16, Yoon SK17, Kim MY18, Lee KS3, Lim YS19, Lee WS20, Han KH3.
Author information
1
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
2
Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
3
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
4
Department of Internal Medicine, Catholic University Medical College St. Vincent, Suwon, 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, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
9
Department of Internal Medicine, Gwangju Christian Hospital, Gwangju, Korea.
10
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
11
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
12
Department of Internal Medicine, Inha University College 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, 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.
Abstract
OBJECTIVES:
Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV).
METHODS:
After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL).
RESULTS:
Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients.
DISCUSSION:
This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.