Safety and efficacy of switching to besifovir dipivoxil maleate in virologically-suppressed chronic hepatitis B patients with tenofovir disoproxil fumarate: 24-week interim analysis

Abstract

Background and aims: Long-term viral suppression is needed for the management of chronic hepatitis B (CHB). Although tenofovir disoproxil fumarate (TDF) shows high antiviral efficacy, its extended use is associated with renal toxicity and bone mineral density reduction. Therefore, we aimed to evaluate the efficacy and safety of besifovir dipivoxil maleate (BSV) for 48 weeks in CHB patients after switching therapy from TDF to BSV. Method: We are currently performing a randomized, activecontrolled, open-label, multicenter study to evaluate safety and non-inferior efficacy of switching from TDF to BSV for 48 weeks compared to continuing TDF in virologically suppressed patients (HBV DNA <20 IU/ml). The primary end point was the proportion of patients who achieve a sustained undetectable HBV DNA level <20 IU/ ml at 48 weeks. We evaluated renal and bone-related outcomes for safety analysis. Results: A total of 153 patients were enrolled. An interim analysis was conducted on a subset of 142 patients (70 switched to BSV, 72 maintaining TDF) at week 24. Baseline characteristics were similar between the two groups. At 24 weeks, high rates of virologic response were maintained 98.6% and 100% in BSV and TDF groups, respectively (95% CI − 4.33 to 1.39; p = 0.493). None of the patients developed virologic breakthrough. The mean eGFR significantly improved by 4.20% in the BSV group (p = 0.003) whereas it changed only by 1.00% in the TDF group (p = 0.482). Patients who switched to BSV experienced improvements in bone turnover biomarkers while those who maintaining TDF worsened, and had increased T-score of bone mineral density at spine (p < 0.001). FIB-4 score declines in the BSV group was larger than in TDF group (p = 0.005). Conclusion: In this interim analysis, patients who switched from TDF to BSV maintained efficacy in viral suppression without virological breakthrough with significant improvements in bone safety at 24 weeks.