Sofosbuvir

Evidence Level: L3

Predicted Indications: 8

Sofosbuvir

Pharmacist Assessment Report

Sofosbuvir: From Chronic Hepatitis C to Hepatitis B Virus Infection

One-Sentence Summary

Sofosbuvir is a nucleotide polymerase inhibitor, originally used to treat chronic hepatitis C virus (HCV) infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, but the supporting data come almost entirely from HCV/HBV co-infection studies. Only 1 small Phase 2 study (n=21) has looked at HBV directly, and there is no clear mechanistic basis for antiviral activity against HBV.

Quick Overview

Item	Content
Original Indication	Chronic hepatitis C virus infection (approved indication text not available in the data compiled)
Predicted New Indication	Hepatitis B virus infection
TxGNN Prediction Score	0.9977
Evidence Level	L3
Australia Market Status	Listed on the PBS Schedule (2 of 2 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	2 (valid: 2)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data for sofosbuvir are not available in the data compiled for this report. From what is known, sofosbuvir is a nucleotide analogue that inhibits the HCV NS5B RNA-dependent RNA polymerase. It is marketed in Australia as part of fixed-dose combinations with velpatasvir (Epclusa) and with velpatasvir plus voxilaprevir (Vosevi).

The mechanistic link to HBV is weak. HBV is a DNA virus that replicates through a reverse-transcriptase step, so sofosbuvir has no established direct activity against it. The clinical data come from HCV/HBV co-infection, where clearing HCV can shift HBV-DNA and HBsAg levels. The main safety concern in that setting is HBV reactivation, and the evidence supports monitoring or prophylaxis (for example with tenofovir alafenamide) rather than using sofosbuvir to treat HBV. The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence or a proven treatment effect.

The single most relevant study is a Phase 2 open-label trial of ledipasvir/sofosbuvir in HBV mono-infection, which was based on a modest HBsAg reduction seen retrospectively in co-infected patients.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT03312023	Phase 2	Completed	21	Ledipasvir/sofosbuvir for 12 weeks in HBV-infected subjects; single-arm and small, so it can only show HBV behaviour and safety, not efficacy
NCT02555943	Phase 2/3	Completed	23	DAAs in HCV/HBV co-infection; focus on HBV reactivation during anti-HCV treatment
NCT04997564	Phase 4	Unknown	120	SOF/VEL with prophylactic TAF in HCV/HBV co-infection; tests prevention of HBV reactivation
NCT03186313	Phase 3	Completed	72	Randomised sofosbuvir-based combinations in genotype 4 HCV; efficacy target is HCV
NCT02483156	Phase 2/3	Completed	80	Sofosbuvir plus ribavirin in genotype 4 HCV; HBV link is through the study population
NCT03549312	Phase 4	Unknown	25	HIV/HCV switch feasibility study; HBV relevance is incidental

No ANZCTR identifiers were available in the data compiled.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
36045503	2023	Phase 2 open-label trial	J Med Virol	Ledipasvir/sofosbuvir in HBV mono-infection, with HBsAg and HBV DNA decline as endpoints
42558970	2026	Clinical study	J Clin Transl Hepatol	Safety and efficacy of SOF/VEL with TAF pre-treatment in HBV/HCV co-infection, assessing HBV reactivation
35268497	2022	Cohort	J Clin Med	Different HBV-DNA and HBsAg kinetics in HCV co-infected patients during DAA therapy
33523503	2021	Prospective observational	J Viral Hepat	HBV reactivation in cancer patients receiving DAAs for HCV
26967675	2016	Review	J Clin Virol	HBV reactivation as a challenge during DAA treatment of HCV
31542053	2019	Case report	J Med Case Rep	HBV reactivation with an immune-escape mutant during sofosbuvir/velpatasvir treatment
27621502	2015	Case report	Hosp Pharm	HBV reactivation with simeprevir plus sofosbuvir
25027705	2014	Review	Minerva Gastroenterol Dietol	Antivirals for hepatitis B and C and their effects on kidney function

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 11144M	Epclusa	Tablet containing 400 mg sofosbuvir with 100 mg velpatasvir	Not available in the data compiled
ARTG 11658N	Vosevi	Tablet containing 400 mg sofosbuvir with 100 mg velpatasvir and 100 mg voxilaprevir	Not available in the data compiled

Safety Considerations

Drug Interactions (8 interactions recorded):
- Major: apalutamide, enzalutamide, lorlatinib
- Moderate: fostamatinib, warfarin, dicoumarol, encorafenib
- Minor: cyclosporine
HBV reactivation: The literature in this report repeatedly shows that HBV can reactivate when HCV is cleared with direct-acting antivirals in co-infected patients. This is directly relevant to any HBV-related use.

For other warnings and contraindications, please refer to the TGA-approved Product Information (PI).

Conclusion and Next Steps

Decision: Hold

Rationale: There is no mechanistic basis for direct anti-HBV activity, and the clinical evidence is limited to HCV/HBV co-infection plus one small, single-arm Phase 2 study. The data point towards HBV reactivation risk and monitoring rather than treatment benefit.

To proceed, the following is needed:

Mechanism of action data and any in vitro evidence of anti-HBV activity
Controlled studies of HBV efficacy in HBV mono-infection, with virological endpoints (HBsAg, HBV DNA)
Approved indication text and PI safety information (warnings, contraindications) for the Australian products
A monitoring or prophylaxis plan for HBV reactivation in co-infected patients
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.