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

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 a Authors share co-first authorship.

New Approaches to the Treatment of Chronic Hepatitis B

“…Novel NAs are under development aiming to improve on efficacy from existing ones. For example, besifovir [ 20 ] and prodrugs of tenofovir comprising tenofovir exalidex [ 21 ], tenofovir disoproxil orotate [ 22 ], and metacavir [ 23 ] are currently under investigation. However, it is clear that the optimal strategy should aim at targeting multiple steps in the HBV life cycle, so that HBV replication is suppressed and formation of new cccDNA is inhibited.…”

Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop

“…[40][41][42] Additionally, newer generation drugs (besifovir dipivoxil maleate [besifovir] and tenofovir alafenamide fumarate [tenofovir AF]) have alleviated the safety concerns associated with tenofovir DF (renal and bone toxicity), while maintaining a high genetic barrier to resistance. [43][44][45] Therefore, the KASL recommends NAs with a high genetic barrier to resistance, including entecavir, tenofovir DF, tenofovir AF, and besifovir, rather than those with a low genetic barrier to resistance (lamivudine, telbivudine, clevudine, and adefovir) as first-line agents for CHB treatment. 9 Lamivudine and adefovir have been used for extended periods but are no longer recommended given their low potency and high incidence of resistance.…”

“…44,45 Besifovir is an acyclic nucleotide phosphonate developed in Korea that was approved by the Ministry of Food and Drug Safety in 2017. 43 However, it is still not available outside Korea. The KASL guidelines are the first to include besifovir as one of the initial choices for CHB treatment.…”

“…9 The advantage of besifovir over teno-fovir DF has been well described. 43 Briefly, in phase 3 randomized controlled trials, besifovir was comparable to tenofovir DF in terms of antiviral efficacy after 48 weeks of treatment. Additionally, the renal and bone safety profiles of besifovir were superior to those of tenofovir DF.…”

Issue Highlights

“…S everal recent papers in Clinical Gastroenterology and Hepatology have reported data on the effectiveness of antiviral treatment in improving outcomes of patients with chronic hepatitis B virus infection. [11][12][13][14] However, there are limited data on the clinical outcomes and safety associated with long-term treatment. In this issue of Clinical Gastroenterology and Hepatology, Hou et al 15 describe longterm clinical and virological outcomes from a randomized study of over 12,000 patients with HBV who were treated with either entecavir or other nucleos(t)ide analogues for up to 10 years in 299 centers across the world.…”