Velpatasvir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Velpatasvir: From Chronic Hepatitis C to Hepatitis B Virus Infection
One-Sentence Summary
Velpatasvir is an HCV NS5A inhibitor, originally used to treat chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection with a very high score, but the data compiled for this report show no trial or publication demonstrating anti-HBV activity. The 5 listed trials and 20 publications concern HCV treatment (including HCV/HBV co-infection), so the prediction rests on the model alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, velpatasvir is an HCV NS5A inhibitor, used in fixed-dose combinations with sofosbuvir (Epclusa) and with sofosbuvir plus voxilaprevir (Vosevi). Its efficacy in hepatitis C is well established.
Mechanistically, the link to hepatitis B is weak. HBV has no NS5A homolog, so velpatasvir has no known direct target in this virus. The very high TxGNN score most likely reflects proximity between viral hepatitis nodes in the knowledge graph rather than a shared target.
The one clinically relevant HBV signal is a safety issue: HBV reactivation has been reported in patients with HBV/HCV co-infection treated with direct-acting antivirals. This is a risk to manage, not a therapeutic effect.
The other top-ranked predictions (hepatitis E, hepatitis A, Omsk hemorrhagic fever, Kyasanur forest disease, HIV, and others) have no direct supporting evidence either. They are not evaluated further here.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04997564 | Phase 4 | Unknown | 120 | 12-week sofosbuvir/velpatasvir with prophylactic tenofovir alafenamide (TAF) in HCV/HBV co-infected adults. TAF is the anti-HBV agent, so this tests prevention of HBV reactivation, not velpatasvir activity against HBV. |
| NCT03549312 | Phase 4 | Unknown | 25 | Pilot feasibility study of sofosbuvir/velpatasvir for HCV within an HIV regimen switch in patients on opioid substitution therapy. No HBV efficacy endpoint. |
| NCT02836925 | Phase 2 | Completed | 40 | Ledipasvir- or velpatasvir-based sofosbuvir therapy for HCV-associated indolent B-cell lymphoma. No anti-HBV activity shown. |
| NCT03579576 | N/A | Completed | 803 | Simplified HCV testing and treatment model in Myanmar, integrated with HIV care. No HBV efficacy endpoint. |
| NCT07560046 | Phase 4 | Not yet recruiting | 1280 | Cluster randomized point-of-care HCV test-and-treat trial in key populations. No HBV efficacy endpoint. |
None of these trials evaluates velpatasvir as a treatment for HBV.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31542053 | 2019 | Case report | J Med Case Rep | HBV reactivation with an HBsAg immune-escape mutant in an anti-HBc-positive patient during sofosbuvir/velpatasvir treatment for HCV. This is a safety signal. |
| 32935438 | 2021 | Study | J Viral Hepat | Simplified sofosbuvir/velpatasvir strategy in Myanmar, including HIV and/or HBV co-infected patients. HBV co-infected participants were treated concurrently with tenofovir. |
| 39735164 | 2024 | Real-world study | J Virus Erad | Effectiveness and safety of sofosbuvir/velpatasvir in Chinese HCV patients, including HCV/HBV co-infection. |
| 35248213 | 2022 | Single-arm trial (cohort) | Lancet Gastroenterol Hepatol | Sofosbuvir/velpatasvir in treatment-naive HCV genotype 4 patients in Rwanda (SHARED-3). HCV efficacy only. |
| 35248212 | 2022 | Single-arm trial (cohort) | Lancet Gastroenterol Hepatol | Sofosbuvir/velpatasvir/voxilaprevir re-treatment after DAA failure in Rwanda. HCV efficacy only. |
| 35579223 | 2022 | Review | Eur J Gen Pract | Overview of HCV diagnosis and treatment. |
| 31041789 | 2019 | Review | Semin Liver Dis | Retreatment of HCV patients after DAA failure. |
| 34092970 | 2021 | Review | World J Gastroenterol | Management of pediatric viral hepatitis B and C. It notes that HBV treatment remains far from curative. |
All of these concern HCV treatment. None shows that velpatasvir is effective against HBV.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15351P | EPCLUSA TABLET 400MG/100MG | Film-coated tablet | Not specified in the data compiled |
| SIN15705P | VOSEVI FILM-COATED TABLETS 400MG/100MG/100MG | Film-coated tablet | Not specified in the data compiled |
Safety Considerations
- Drug Interactions: 57 interactions were identified. Major interactions include:
- Proton pump inhibitors: omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole
- Dexamethasone
Moderate interactions include antacids (aluminum hydroxide, calcium carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate, magaldrate), H2 blockers (cimetidine, famotidine, nizatidine), and naldemedine.
- HBV reactivation: Reactivation has been reported in HBV/HCV co-infected patients during DAA therapy (see PMID 31542053). HBV status should be screened before use.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score is not backed by any mechanism or clinical data. HBV has no NS5A target, and every trial and publication retrieved concerns HCV. The only HBV-related signal is a reactivation risk during HCV therapy, which is a safety concern rather than a benefit.
To proceed, the following is needed:
- In vitro evidence of velpatasvir activity against HBV
- Mechanism of action data (MOA)
- Package insert warnings and contraindications from the Health Sciences Authority (HSA)
- If pursued, a plan for HBV screening and reactivation monitoring 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.