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

Research output: Contribution to journalArticle

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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

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Tenofovir
Chronic Hepatitis B
Virus Diseases
Hepatitis B virus
Safety
Bone Density
Therapeutics
Glomerular Filtration Rate
Antiviral Agents
((1-((2-amino-9H-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonic acid dipivoxyl
maleic acid
Pelvic Bones
Kidney
Republic of Korea

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Ahn, Sang Hoon ; Kim, Won ; Jung, Young Kul ; Yang, Jin Mo ; Jang, Jae Young ; Kweon, Yong Oh ; Cho, Yong Kyun ; Kim, Yoon Jun ; Hong, Gun Young ; Kim, Dong Joon ; Um, Soon Ho ; Sohn, Joo Hyun ; Lee, Jin Woo ; Park, Sung Jae ; Lee, Byung Seok ; Kim, Ju Hyun ; Kim, Hong Soo ; Yoon, Seung Kew ; Kim, Moon Young ; Yim, Hyung Joon ; Lee, Kwan Sik ; Lim, Young Suk ; Lee, Wan Sik ; Park, Neung Hwa ; Jin, So Young ; Kim, Kyun Hwan ; Choi, Won ; Han, Kwang Hyub. / Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection. In: Clinical Gastroenterology and Hepatology. 2019 ; Vol. 17, No. 9. pp. 1850-1859.e4.
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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.",
author = "Ahn, {Sang Hoon} and Won Kim and Jung, {Young Kul} and Yang, {Jin Mo} and Jang, {Jae Young} and Kweon, {Yong Oh} and Cho, {Yong Kyun} and Kim, {Yoon Jun} and Hong, {Gun Young} and Kim, {Dong Joon} and Um, {Soon Ho} and Sohn, {Joo Hyun} and Lee, {Jin Woo} and Park, {Sung Jae} and Lee, {Byung Seok} and Kim, {Ju Hyun} and Kim, {Hong Soo} and Yoon, {Seung Kew} and Kim, {Moon Young} and Yim, {Hyung Joon} and Lee, {Kwan Sik} and Lim, {Young Suk} and Lee, {Wan Sik} and Park, {Neung Hwa} and Jin, {So Young} and Kim, {Kyun Hwan} and Won Choi and Han, {Kwang Hyub}",
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Ahn, SH, Kim, W, Jung, YK, Yang, JM, Jang, JY, Kweon, YO, Cho, YK, Kim, YJ, Hong, GY, Kim, DJ, Um, SH, Sohn, JH, Lee, JW, Park, SJ, Lee, BS, Kim, JH, Kim, HS, Yoon, SK, Kim, MY, Yim, HJ, Lee, KS, Lim, YS, Lee, WS, Park, NH, Jin, SY, Kim, KH, Choi, W & Han, KH 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, vol. 17, no. 9, pp. 1850-1859.e4. https://doi.org/10.1016/j.cgh.2018.11.001

Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection. / Ahn, Sang Hoon; Kim, Won; Jung, Young Kul; Yang, Jin Mo; Jang, Jae Young; Kweon, Yong Oh; Cho, Yong Kyun; Kim, Yoon Jun; Hong, Gun Young; Kim, Dong Joon; Um, Soon Ho; Sohn, Joo Hyun; Lee, Jin Woo; Park, Sung Jae; Lee, Byung Seok; Kim, Ju Hyun; Kim, Hong Soo; Yoon, Seung Kew; Kim, Moon Young; Yim, Hyung Joon; Lee, Kwan Sik; Lim, Young Suk; Lee, Wan Sik; Park, Neung Hwa; Jin, So Young; Kim, Kyun Hwan; Choi, Won; Han, Kwang Hyub.

In: Clinical Gastroenterology and Hepatology, Vol. 17, No. 9, 08.2019, p. 1850-1859.e4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection

AU - Ahn, Sang Hoon

AU - Kim, Won

AU - Jung, Young Kul

AU - Yang, Jin Mo

AU - Jang, Jae Young

AU - Kweon, Yong Oh

AU - Cho, Yong Kyun

AU - Kim, Yoon Jun

AU - Hong, Gun Young

AU - Kim, Dong Joon

AU - Um, Soon Ho

AU - Sohn, Joo Hyun

AU - Lee, Jin Woo

AU - Park, Sung Jae

AU - Lee, Byung Seok

AU - Kim, Ju Hyun

AU - Kim, Hong Soo

AU - Yoon, Seung Kew

AU - Kim, Moon Young

AU - Yim, Hyung Joon

AU - Lee, Kwan Sik

AU - Lim, Young Suk

AU - Lee, Wan Sik

AU - Park, Neung Hwa

AU - Jin, So Young

AU - Kim, Kyun Hwan

AU - Choi, Won

AU - Han, Kwang Hyub

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

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