Voxilaprevir
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Voxilaprevir: Hepatitis B virus infection
One-Sentence Summary
Voxilaprevir is an HCV NS3/4A protease inhibitor, originally used (as part of a fixed-dose combination with sofosbuvir and velpatasvir) to treat chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, but there are no clinical trials and no publications that actually test voxilaprevir against HBV, so the prediction rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 0.9984 |
| Evidence Level | L5 (the data compiled for this report assigns L4, but none of the retrieved publications tests voxilaprevir in HBV, so L5 is the more accurate level) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available from the compiled data. Based on known information, voxilaprevir is an HCV NS3/4A serine protease inhibitor, used in combination with sofosbuvir (an NS5B polymerase inhibitor) and velpatasvir (an NS5A inhibitor). Its efficacy in HCV, including retreatment after failure of other direct-acting antivirals, is well established.
A direct mechanistic link to HBV is not supported. HBV replicates through a reverse transcriptase/polymerase and a core-capsid-based process and has no NS3/4A-like protease. The very high TxGNN score most likely reflects network proximity within the viral hepatitis category rather than a pharmacological rationale. HBV matters for voxilaprevir mainly as a safety issue: HBV reactivation is a recognised risk during DAA therapy in HCV/HBV co-infected patients. That is not a therapeutic effect.
Other predictions (ranks 2–10) were also reviewed. Hepatitis A, hepatitis E, HIV and the animal-model conditions all lack a plausible direct mechanism, and none has trial or literature evidence of voxilaprevir activity. Omsk haemorrhagic fever and Kyasanur forest disease involve flaviviruses related to HCV, so NS3 protease homology offers a speculative rationale, but there is no supporting data.
Clinical Trial Evidence
Currently no related clinical trials are registered for hepatitis B virus infection.
Literature Evidence
None of the nine retrieved publications tests voxilaprevir against HBV. They concern HCV and are listed only for context.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35248212 | 2022 | Single-arm trial (cohort) | Lancet Gastroenterol Hepatol | SOF/VEL/VOX retreatment of HCV after prior DAA failure in Rwanda (SHARED-3) |
| 36535062 | 2022 | Cohort | J Gastrointestin Liver Dis | Real-world SOF/VEL/VOX in Romanian genotype 1b patients who did not respond to earlier DAAs |
| 31041789 | 2019 | Review | Semin Liver Dis | Retreatment of HCV patients after DAA failure |
| 31114957 | 2019 | Review | Clin Pharmacokinet | Pharmacokinetic and pharmacodynamic considerations for HCV therapy |
| 30964552 | 2019 | Preclinical/virology | Hepatology | Resistance patterns of HCV protease inhibitor escape variants |
| 40611935 | 2025 | Cohort | J Clin Exp Hepatol | Resistance-associated substitutions and predictors of DAA treatment failure in an HCV elimination programme |
| 29369303 | 2018 | Conference report | AIDS Rev | Summary of the International Conference on Viral Hepatitis 2017 |
| 40414600 | 2025 | Economic analysis | Ann Hepatol | International comparison of HBV and HCV drug prices |
| 41570233 | 2025 | Epidemiology | Vopr Virusol | Prevalence of HIV, HBV and HCV markers among dental patients |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11658N | Vosevi | Tablet containing 400 mg sofosbuvir with 100 mg velpatasvir and 100 mg voxilaprevir (oral) | Indication text not recorded in the data compiled for this report |
Safety Considerations
- Drug Interactions: 19 interacting drugs were identified (Moderate and Major). The Major-level interactions are:
- Rosuvastatin
- Edoxaban
- Cyclosporine
Moderate-level interactions include:
- Apixaban
- Cobicistat
- Ethinylestradiol
- Eltrombopag
- Obeticholic acid
- Eluxadoline
- Several oncology agents (afatinib, bosutinib, cobimetinib, idelalisib, lapatinib, lenvatinib, olaparib, pazopanib)
- Artesunate
- Teriflunomide
- HBV reactivation: In HCV/HBV co-infected patients, HBV reactivation is a recognised risk during DAA therapy. This is a safety consideration and does not indicate benefit against HBV.
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by a high model score. HBV has no NS3/4A-like protease target, no trial or publication tests voxilaprevir in HBV, and no other predicted indication has credible supporting evidence either.
To proceed, the following is needed:
- In vitro antiviral activity data for voxilaprevir against HBV
- Mechanism of action data (MOA) to test any plausible link
- TGA Product Information warnings and contraindications for safety screening
- A review of HBV reactivation risk and monitoring in HCV/HBV co-infected patients
- If any new indication is pursued, an interaction-management plan covering the Major-level interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.