Clin Gastroenterol Hepatol. 2018 Nov 15. pii: S1542-3565(18)31244-8. doi: 10.1016/j.cgh.2018.11.001. [Epub ahead of print]
Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic HBV Infection.
Ahn SH1, Kim W2, Jung YK3, Yang JM4, Jang JY5, Kweon YO6, Cho YK7, Kim YJ8, Hong GY9, Kim DJ10, Um SH3, Sohn JH11, Lee JW12, Park SJ13, Lee BS14, Kim JH15, Kim HS16, Yoon SK17, Kim MY18, Yim HJ3, Lee KS1, Lim YS19, Lee WS20, Park NH21, Jin SY5, Kim KH22, Choi W23, Han KH24.
Author information
1
Department of Internal Medicine, Yonsei 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, Korea University College of Medicine, Seoul, Korea.
4
Department of Internal Medicine, Catholic University Medical College St. Vincent's Hospital, 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, 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, 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, Pusan, 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.
21
Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan, Korea.
22
Department of Pharmacology, School of Medicine, Konkuk University, Korea.
23
Ildong Pharmaceutical Co., Ltd., Seoul, Korea.
24
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address: [email protected].
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.
Antiviral therapy; Bone mineral density; Drug resistance; Hepatitis B; Nephrotoxicity; acyclic nucleotide phosphonate; drug resistance; eGFR; nephrotoxicity