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, but the 5 clinical trials and 22 publications found all concern HCV, so this prediction currently rests on the model alone, without direct supporting evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 0.9987 |
| Evidence Level | L4 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from the compiled data. Based on known information, velpatasvir is an HCV NS5A inhibitor and is 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 protein, so velpatasvir has no direct target in this virus. The high score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, such as the two “viral hepatitis” diseases, not biological evidence or a shared drug target.
The available HBV-related evidence also does not show benefit. One trial addresses HBV reactivation management in HCV/HBV co-infected patients, and any protective effect there comes from tenofovir alafenamide (TAF), not velpatasvir. One case report describes HBV reactivation during sofosbuvir/velpatasvir treatment, which is a safety signal rather than evidence of benefit.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04997564 | Phase 4 | Unknown | 120 | 12-week SOF/VEL with prophylactic TAF in HCV/HBV co-infection. It addresses HBV reactivation, but benefit is attributable to TAF. |
| NCT03549312 | Phase 4 | Unknown | 25 | Switch to E/C/F/TAF, then SOF/VEL for HCV, in HIV/HCV co-infected patients on opioid substitution therapy. Any anti-HBV effect comes from TAF. |
| NCT02836925 | Phase 2 | Completed | 40 | Interferon-free DAA therapy in HCV-associated indolent B-cell lymphoma. No HBV endpoint. |
| NCT03579576 | N/A | Completed | 803 | Simplified HCV testing and treatment model in Myanmar. HBV is not the studied indication. |
| NCT07560046 | Phase 4 | Not yet recruiting | 1280 | Cluster randomized trial of point-of-care HCV testing and treatment. No HBV efficacy data. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42558970 | 2026 | Multicenter study | J Clin Transl Hepatol | Safety and efficacy of SOF/VEL with TAF pre-treatment on HBV reactivation in HBV/HCV co-infection. |
| 31542053 | 2019 | Case report | J Med Case Rep | HBV reactivation with a surface-antigen immune-escape mutant during SOF/VEL treatment for HCV (a safety signal). |
| 32935438 | 2021 | Cohort | J Viral Hepat | Simplified HCV treatment in Myanmar, including HBV co-infected patients treated concurrently with tenofovir. |
| 39735164 | 2024 | Real-world study | J Virus Eradication | Real-life SOF/VEL effectiveness in Chinese HCV patients, including HCV/HBV co-infection. |
| 34092970 | 2021 | Review | World J Gastroenterol | Management of paediatric viral hepatitis. Notes HBV treatment is far from curative. |
| 35248213 | 2022 | Single-arm trial | Lancet Gastroenterol Hepatol | SOF/VEL in treatment-naive HCV in Rwanda (SHARED-3). |
| 31114957 | 2019 | Review | Clin Pharmacokinet | Pharmacokinetic and pharmacodynamic considerations of HCV therapy. |
| 41734217 | 2025 | Retrospective study | Klin Mikrobiol Infekc Lek | Antiviral treatment of chronic hepatitis B and C in children in Ostrava. |
None of these publications shows that velpatasvir treats HBV.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02456370 | EPCLUSA | Not specified | Not specified |
| 02467542 | VOSEVI | Not specified | Not specified |
Safety Considerations
- Drug Interactions: 57 interactions were identified. The main ones from the compiled data:
- Major: dexamethasone and the proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole).
- Moderate: antacids (aluminum hydroxide, calcium carbonate, magaldrate, magnesium carbonate, magnesium hydroxide, magnesium oxide), H2 blockers (cimetidine, famotidine, nizatidine) and naldemedine.
- Minor: fidaxomicin, naloxegol and prucalopride.
- HBV reactivation: A case report describes HBV reactivation during SOF/VEL therapy in an HBV core antibody-positive patient. Any HBV-related use would need careful monitoring and antiviral cover.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high (0.9987), but it appears to reflect network proximity between viral hepatitis diseases. Velpatasvir targets HCV NS5A, which HBV lacks. All trials and publications found are HCV studies, and the HBV-related data are about co-infection management or reactivation risk, not anti-HBV efficacy.
To proceed, the following is needed:
- Mechanism of action data and in vitro evidence of anti-HBV activity
- Preclinical or early clinical data showing an HBV virological effect
- Health Canada package insert warnings and contraindications
- A reactivation risk-management plan for HBV co-infected patients
Other predicted indications: The remaining nine predictions (hepatitis E, hepatitis A, animal viral hepatitis, Omsk hemorrhagic fever, Kyasanur forest disease, HIV, simian immunodeficiency virus infection, feline immunodeficiency syndrome and a rare neurodevelopmental disorder) have no direct efficacy evidence and are also rated Hold. For HIV, the available data concern HCV treatment in co-infected patients and drug interactions with antiretrovirals, not HIV treatment.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.