Velpatasvir

Evidence Level: L4

Predicted Indications: 10

Velpatasvir

Pharmacist Assessment Report

Velpatasvir: From Chronic Hepatitis C to Hepatitis B Virus Infection

One-Sentence Summary

Velpatasvir is an HCV NS5A inhibitor, used in fixed-dose combinations with sofosbuvir (and with voxilaprevir) to treat chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, but the supporting evidence is weak. The 5 linked clinical trials and literature concern HCV treatment or HBV reactivation safety, not HBV efficacy of velpatasvir.

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
Australia Market Status	Listed on the PBS Schedule (2 of 2 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	2 (valid: 2)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available. Based on known information, velpatasvir is part of the sofosbuvir/velpatasvir combination (and the sofosbuvir/velpatasvir/voxilaprevir combination). It acts as an HCV NS5A inhibitor, and its efficacy in chronic hepatitis C is well established.

The link to HBV is weak. HBV is a DNA virus that replicates via reverse transcription, and velpatasvir has no established activity against it. The very high TxGNN score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.

The related trials do not support an anti-HBV effect. In the trial of SOF/VEL with prophylactic tenofovir alafenamide (TAF), the HBV protection comes from TAF. The literature on HBV in this setting concerns HBV reactivation during HCV direct-acting antiviral treatment, which is a safety concern rather than a treatment indication.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT04997564	Phase 4	Unknown	120	12-week SOF/VEL with prophylactic TAF in HCV/HBV co-infected adults. TAF provides the HBV protection, so it shows nothing about velpatasvir’s anti-HBV efficacy
NCT03549312	Phase 4	Unknown	25	Switch to E/C/F/TAF, then SOF/VEL, in HIV-HCV co-infected patients on opioid substitution therapy. Indirect; the HBV-active component is TAF
NCT02836925	Phase 2	Completed	40	Interferon-free HCV therapy in HCV-associated indolent B-cell lymphoma. Not relevant to HBV
NCT03579576	N/A	Completed	803	Simplified HCV testing and treatment in Myanmar. HCV only
NCT07560046	Phase 4	Not yet recruiting	1280	Point-of-care HCV test-and-treat cluster trial. No HBV efficacy endpoint

No trial evaluates velpatasvir for HBV efficacy.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
31542053	2019	Case report	J Med Case Rep	HBV reactivation with an HBsAg immune-escape mutant during SOF/VEL treatment in an anti-HBc positive patient
42558970	2026	Multicentre study	J Clin Transl Hepatol	Safety and efficacy of SOF/VEL with TAF pre-treatment on HBV reactivation in HBV/HCV co-infection
32935438	2021	Cohort	J Viral Hepat	Simplified HCV treatment in Myanmar; HBV co-infected patients received concurrent tenofovir
39735164	2024	Real-world study	J Virus Erad	Real-world SOF/VEL effectiveness in Chinese HCV patients, including HCV/HBV co-infection
34092970	2021	Review	World J Gastroenterol	Management of paediatric viral hepatitis B and C; HBV treatment remains non-curative
35248213	2022	Single-arm trial	Lancet Gastroenterol Hepatol	SOF/VEL in treatment-naive HCV patients in Rwanda (SHARED-3)
31041789	2019	Review	Semin Liver Dis	Retreatment of HCV patients after direct-acting antiviral failure

The literature supports HCV use and HBV reactivation risk only. It does not show anti-HBV activity of velpatasvir.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 11144M	Epclusa	Tablet containing 400 mg sofosbuvir with 100 mg velpatasvir	Not listed in the data compiled
ARTG 11658N	Vosevi	Tablet containing 400 mg sofosbuvir with 100 mg velpatasvir and 100 mg voxilaprevir	Not listed in the data compiled

Safety Considerations

Drug Interactions: 57 interactions are recorded. Examples include:
- Major: dexamethasone and the proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole)
- Moderate: antacids (aluminium hydroxide, calcium carbonate, magnesium hydroxide, magnesium oxide, magnesium carbonate, magaldrate), H2 blockers (cimetidine, famotidine, nizatidine) and naldemedine
- Minor: fidaxomicin, naloxegol and prucalopride
HBV reactivation: The literature describes HBV reactivation during HCV direct-acting antiviral therapy in patients with past or current HBV infection. This is directly relevant to any HBV-related use.

Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: Velpatasvir has no established anti-HBV activity. The high TxGNN score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. Every linked trial and paper concerns HCV treatment or HBV reactivation safety. No study supports velpatasvir for HBV, so the evidence level is L4 at best.

To proceed, the following is needed:

Mechanism of action data, and in vitro evidence of anti-HBV activity
Preclinical or early-phase studies of velpatasvir against HBV
Approved indication text and PI safety information (warnings and contraindications) for the Australian products
For HCV/HBV co-infection, guidance on HBV screening and monitoring (and antiviral prophylaxis) during SOF/VEL therapy, which is a safety management question rather than a new indication
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.