Pradefovir mesylate and tenofovir amibufenamide for chronic hepatitis B: a systematic review and pragmatic treatment algorithm

Vollständiger Abstract

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Background Pradefovir mesylate (PDV; approved in China in 2024) and tenofovir amibufenamide (TMF; approved in China in 2021) are novel hepatocyte-targeted nucleotide prodrugs recently approved in China. Their clinical positioning relative to the guideline-endorsed benchmark tenofovir alafenamide (TAF) for chronic hepatitis B management remains undefined, particularly regarding renal/bone safety and drug-drug interaction profiles. Objective To synthesize available evidence and propose a pragmatic treatment selection framework. Methods Narrative review with systematic literature search of Phase 2/3 randomized trials and observational real-world cohort studies (≥48 weeks follow-up, n ≥ 100) comparing PDV or TMF with TDF or TAF, with explicit evidence quality classification. Methods: Systematic review with qualitative synthesis of Phase 2/3 trials and observational cohorts comparing PDV or TMF with TDF or TAF. Risk of bias (RoB 2, NOS) and GRADE certainty were assessed. Results TMF demonstrated noninferior antiviral efficacy versus TDF through Week 96 with superior renal and bone safety. TMF demonstrated noninferior antiviral efficacy versus TDF through Week 96, with improved renal and bone safety profiles compared with TDF. Retrospective real-world comparisons suggest comparable efficacy to TAF; however, prospective confirmation is needed. PDV demonstrated comparable HBV DNA suppression to TDF at Week 24, with sustained efficacy and favorable safety through Week 96 in Phase 3 trials PDV showed comparable HBV DNA suppression to TDF at Week 24, with Phase 3 data at Weeks 48 and 96 now available in Chinese CHB patients. PDV’s CYP3A4-dependent activation creates clinically significant drug-drug interaction potential, whereas TMF and TAF utilize non-CYP pathways with favorable interaction profiles. PDV’s CYP3A4-dependent activation raises the theoretical possibility of drug-drug interactions based on in vitro metabolic data, whereas TMF and TAF utilize non-CYP pathways with favorable interaction profiles. Conclusion Based on currently available evidence, TMF represents a potentially viable TAF alternative for patients with renal/bone risk or anticipated long-term therapy, though definitive therapeutic equivalence requires prospective head-to-head randomized trials. PDV remains an emerging option requiring cautious implementation pending further characterization of its long-term durability, resistance barrier, and drug-drug interaction profile. Conclusion: TMF may represent an alternative to TAF for patients with renal/bone risk or anticipated long-term therapy, though definitive equivalence requires prospective head-to-head randomized trials. PDV offers comparable short-term efficacy to TDF, with longer-term data now available; continued follow-up will define its role among nucleotide prodrugs.