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, originally used (as part of the Vosevi combination) 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 9 publications are linked to this prediction, and none of those publications studies anti-HBV activity. The evidence is indirect only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus (HCV) infection in patients aged 12 years and older and weighing at least 30 kg |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L4 |
| EU Market Status | Cancelled only (no currently valid authorization) |
| Number of Authorizations | 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 information, voxilaprevir is an HCV NS3/4A protease inhibitor used in the Vosevi combination, and its efficacy in chronic hepatitis C is well established.
The prediction is not mechanistically supported. HBV has no NS3/4A protease. It replicates through a reverse transcriptase/polymerase and a different replication cycle, so there is no plausible direct target overlap. The high TxGNN score most likely reflects network proximity between hepatitis C and other hepatotropic viral diseases in the knowledge graph, not a shared drug target.
The retrieved literature concerns HCV retreatment, and HBV appears only incidentally (drug pricing, dental bloodborne-infection markers, a conference report). There is no direct evidence of anti-HBV activity. The other top-ranked predictions (hepatitis E, hepatitis A, flavivirus diseases, HIV and related) are similarly weak: none has a clear mechanistic link, and the trials linked to them are HCV or HIV/HCV studies.
Clinical Trial Evidence
Currently no related clinical trials are registered for hepatitis B virus infection.
Literature Evidence
None of these publications evaluates voxilaprevir against HBV. They describe HCV treatment, and HBV is mentioned only incidentally.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35248212 | 2022 | Single-arm trial (cohort) | Lancet Gastroenterol Hepatol | Sofosbuvir-velpatasvir-voxilaprevir re-treatment of HCV after prior DAA failure in Rwanda (SHARED-3) |
| 36535062 | 2022 | Cohort | J Gastrointestin Liver Dis | Real-world efficacy and safety of sofosbuvir-velpatasvir-voxilaprevir in Romanian genotype 1b patients who did not respond to prior DAAs |
| 31041789 | 2019 | Review | Semin Liver Dis | Retreatment of HCV patients after DAA failure |
| 31114957 | 2019 | Review | Clin Pharmacokinet | Pharmacokinetic and pharmacodynamic considerations of HCV therapy, 2019 update |
| 40611935 | 2025 | Cohort | J Clin Exp Hepatol | Resistance-associated substitutions and predictors of DAA treatment failure in an HCV elimination programme |
| 30964552 | 2019 | Preclinical/Virology | Hepatology | Evolution and persistence of HCV protease inhibitor resistance variants |
| 29369303 | 2018 | Conference report | AIDS Rev | International Conference on Viral Hepatitis 2017; HBV and HCV burden and treatment discussed |
| 40414600 | 2025 | Economic analysis | Ann Hepatol | Global comparison of HBV and HCV drug pricing |
| 41570233 | 2025 | Cross-sectional | Vopr Virusol | Prevalence of HIV, HBV and HCV markers among dental patients |
EU Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| EMEA/H/C/004350 | Vosevi | Not specified | Treatment of chronic hepatitis C virus (HCV) infection in patients aged 12 years and older and weighing at least 30 kg. (see sections 4.2, 4.4 and 5.1). |
The authorization is cancelled, so there is currently no valid EU marketing authorization.
Safety Considerations
- Drug Interactions: 19 interactions were identified in DDInter. Major-level interactions are:
- Rosuvastatin
- Edoxaban
- Cyclosporine
The remaining 16 are Moderate level, including cobicistat, apixaban, eltrombopag, ethinylestradiol, obeticholic acid, eluxadoline, artesunate, afatinib, bosutinib, cobimetinib, idelalisib, lapatinib, lenvatinib, olaparib, pazopanib and teriflunomide.
- Other: HBV reactivation is a known risk during HCV direct-acting antiviral therapy. This matters for any use of the drug in patients with HBV.
Please refer to the SmPC for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but there is no plausible mechanism (HBV lacks an NS3/4A protease target), no clinical trials and no literature showing anti-HBV activity. The evidence is indirect only. The EU authorization is also cancelled.
To proceed, the following is needed:
- Mechanism of action data for voxilaprevir
- In vitro evidence of anti-HBV activity, for example in HBV replication cell models, to establish any biological basis
- SmPC safety information (warnings and contraindications), especially on HBV reactivation
- A review of whether the other predicted indications (e.g., the HIV/HCV co-infection evidence) offer a more tractable path, since those results concern HCV treatment, not new activity
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.