Voxilaprevir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Voxilaprevir: From Chronic Hepatitis C to Hepatitis B Virus Infection
One-Sentence Summary
Voxilaprevir is an HCV NS3/4A protease inhibitor, marketed in Singapore as part of a fixed-dose combination (VOSEVI) and originally used to treat chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, but no clinical trials and no publications that test anti-HBV activity currently support this direction. The prediction should be treated as a computational hypothesis only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection (the Singapore licence text carries no approved-indication wording) |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known pharmacology, voxilaprevir is an HCV NS3/4A serine protease inhibitor, and it is used together with sofosbuvir and velpatasvir. Its efficacy in hepatitis C is well established, including in patients who failed earlier direct-acting antivirals.
The link to hepatitis B is weak. HBV does not encode an NS3/4A-like protease. It replicates through a reverse transcriptase/polymerase and cccDNA, so there is no clear direct target overlap. The high TxGNN score most likely reflects network proximity to other viral hepatitis indications, not a shared drug target. The publications retrieved concern HCV retreatment, resistance, pharmacokinetics, pricing, and epidemiology. None report anti-HBV activity, and HBV appears only as background context.
Other top predictions (hepatitis E, hepatitis A, HIV, Omsk hemorrhagic fever, Kyasanur forest disease) have no clear targets either, or only a weak family-level rationale. No trials or literature test voxilaprevir against them.
Clinical Trial Evidence
Currently no related clinical trials registered for hepatitis B virus infection.
Literature Evidence
None of the publications below tests voxilaprevir against HBV. They are HCV studies or reviews, and HBV is mentioned only as context.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31041789 | 2019 | Review | Seminars in Liver Disease | Retreatment of HCV patients after direct-acting antiviral failure |
| 31114957 | 2019 | Review | Clinical Pharmacokinetics | Pharmacokinetic and pharmacodynamic considerations of HCV therapies, including sofosbuvir/velpatasvir/voxilaprevir |
| 29369303 | 2018 | Review | AIDS Reviews | Conference report on viral hepatitis treatment, including pan-genotypic HCV regimens |
| 35248212 | 2022 | Single-arm trial (cohort) | Lancet Gastroenterology & Hepatology | Sofosbuvir-velpatasvir-voxilaprevir for HCV retreatment after DAA failure in Rwanda (SHARED-3) |
| 36535062 | 2022 | Cohort | J Gastrointestin Liver Dis | Real-world efficacy and safety of the combination in Romanian genotype 1b patients who did not respond to DAAs |
| 40611935 | 2025 | Cohort | J Clin Exp Hepatol | Resistance-associated substitutions and predictors of DAA treatment failure in an HCV elimination cohort |
| 30964552 | 2019 | Other | Hepatology | Evolutionary pathways of HCV protease inhibitor resistance |
| 40414600 | 2025 | Other | Annals of Hepatology | Global price comparison of hepatitis B and C antivirals |
| 41570233 | 2025 | Cohort | Voprosy Virusologii | Prevalence of HIV, HBV and HCV markers among dental patients |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15705P | VOSEVI FILM-COATED TABLETS 400MG/100MG/100MG | Film-coated tablet (oral) | Not stated in the licence record |
Safety Considerations
- Drug Interactions: 19 interacting drugs were identified. Major-level interactions are with rosuvastatin, edoxaban and cyclosporine. Moderate-level interactions include eluxadoline, obeticholic acid, cobicistat, apixaban, eltrombopag, artesunate, afatinib, bosutinib, cobimetinib, ethinylestradiol, idelalisib, lapatinib, lenvatinib, olaparib, pazopanib and teriflunomide.
- Other: In patients co-infected with HCV and HBV, HBV reactivation during DAA therapy is a recognised clinical concern. It is a safety issue, not a therapeutic benefit.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high (99.84%), but no clinical trials or publications test voxilaprevir against HBV. HBV has no NS3/4A-like protease target, so the prediction is not mechanistically supported. The other predicted indications are weaker still, with no usable evidence.
To proceed, the following is needed:
- Mechanism-of-action data for voxilaprevir
- In vitro antiviral activity data against HBV, to show whether any activity exists
- Package insert warnings and contraindications from the HSA, for safety screening
- Review of HBV reactivation risk and the major drug interactions, if any HBV-related use is explored
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.