Velpatasvir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Velpatasvir: From Hepatitis C Virus Infection to Hepatitis B Virus Infection
One-Sentence Summary
Velpatasvir is an NS5A inhibitor used clinically as part of the sofosbuvir/velpatasvir fixed-dose combination for chronic hepatitis C virus (HCV) infection. The TxGNN model predicts it may also be effective for Hepatitis B Virus Infection, but the supporting evidence body — 25 clinical trials and 20 publications — is almost entirely composed of HCV-focused studies rather than genuine HBV efficacy data, so this prediction currently sits at evidence level L4 with a Hold recommendation.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus (HCV) infection (as a component of the sofosbuvir/velpatasvir combination; inferred from the trial/literature evidence in this pack, as no EU marketing authorization record exists for velpatasvir as a standalone product) |
| Predicted New Indication | Hepatitis B Virus Infection |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 |
| EU Market Status | Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not recorded at the drug level in this Evidence Pack (flagged as a High-severity data gap, DG002). However, the evidence collected for this candidate consistently describes velpatasvir as an HCV-specific NS5A inhibitor, acting on the NS5A protein within the HCV replication complex. This is the accepted mechanism behind its approved use (as the “VEL” component of sofosbuvir/velpatasvir, marketed as Epclusa) for chronic hepatitis C.
Hepatitis B virus, in contrast, is a partially double-stranded DNA virus that replicates via reverse transcriptase and does not possess an NS5A-homologous protein. There is therefore no direct structural or functional target shared between HCV and HBV that would explain cross-activity of an NS5A inhibitor. Reviewing the clinical trial and literature evidence collected for this pairing confirms this: the overwhelming majority of trials and articles are studies of sofosbuvir/velpatasvir (or related regimens) treating HCV — including in patients who happen to be HBV co-infected — rather than studies evaluating velpatasvir’s antiviral activity against HBV itself.
The one literature record that directly discusses HBV (PMID 31542053, a case report) actually describes HBV reactivation occurring during HCV treatment with sofosbuvir/velpatasvir, which is a safety signal, not evidence of therapeutic benefit against HBV. This pattern — where a drug frequently used in HCV/HBV co-infected populations gets flagged by knowledge-graph models as a candidate for HBV itself — is a known artifact of shared clinical contexts rather than a genuine mechanistic signal, and should be interpreted with caution.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03250910 | Phase 4 | Completed | 228 | Generic velpatasvir + sofosbuvir ± ribavirin for HCV in HIV-coinfected patients; studies HCV outcomes, not HBV (relevance grade C — HCV population only) |
| NCT02938013 | Phase 4 | Completed | 15 | Liver/plasma sampling study of HCV viral kinetics during sofosbuvir/velpatasvir(±voxilaprevir) treatment; no HBV endpoint |
| NCT06180590 | N/A | Recruiting | 200 | Cohort study of Vosevi (SOF/VEL/VOX) in patients who failed prior DAA therapy for HCV; not an HBV trial (relevance grade C) |
| NCT03086044 | Phase 4 | Unknown | 148 | Pilot trial transplanting organs from HCV-positive donors to HCV-negative recipients with post-transplant antiviral prophylaxis; HCV-specific |
| NCT03423641 | N/A | Completed | 33,808 | Large safety comparison of DAA-treated vs. untreated HCV patients; no HBV arm |
| NCT03570112 | N/A | Completed | 40 | Natural history and vertical transmission of chronic HCV in pregnancy, with postpartum sofosbuvir/velpatasvir treatment; HCV only |
| NCT03226717 | N/A | Unknown | 100 | Evaluates effect of DAAs on HCV-associated arthropathy/extrahepatic manifestations; not HBV-related |
| NCT04653818 | Phase 4 | Completed | 84 | RCT on whether DAA use affects HCV-related hepatocellular carcinoma recurrence after ablation; HCV-specific |
| NCT03549312 | Phase 4 | Unknown | 25 | Feasibility study switching HIV-HCV coinfected patients through an antiretroviral regimen sequence including 12 weeks of sofosbuvir/velpatasvir for HCV; not an HBV endpoint |
| NCT05016609 | Phase 4 | Unknown | 1,800 | Cluster-randomized trial of same-visit HCV testing/treatment models among people who inject drugs; HCV-focused |
Note: None of the trials collected for this candidate directly evaluate velpatasvir as a treatment for hepatitis B. All are HCV treatment or HCV-related studies, several conducted in populations with HIV or HBV co-infection where velpatasvir was used solely for the HCV component.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31542053 | 2019 | Case Report | J Med Case Rep | HBV reactivation (via an HBsAg immune-escape mutant) in an anti-HBc-positive patient during sofosbuvir/velpatasvir treatment for HCV — a safety signal, not efficacy evidence for HBV |
| 35248213 | 2022 | Single-arm trial | Lancet Gastroenterol Hepatol | Sofosbuvir/velpatasvir efficacy and safety in treatment-naive HCV genotype 4 patients in Rwanda; no HBV endpoint |
| 35248212 | 2022 | Single-arm trial | Lancet Gastroenterol Hepatol | Sofosbuvir/velpatasvir/voxilaprevir retreatment of HCV genotype 4 non-a/d subtypes after prior DAA failure; HCV-specific |
| 38910758 | 2024 | Cross-sectional study | Cureus | Efficacy of sofosbuvir/velpatasvir for HCV in chronic kidney disease patients; no HBV data |
| 33217040 | 2021 | Cohort study | J Gastroenterol Hepatol | Real-world efficacy/safety of sofosbuvir/velpatasvir in HCV genotype 3, including decompensated cirrhosis and HCC patients; HCV only |
| 35579223 | 2022 | Review | Eur J Gen Pract | General review of chronic HCV diagnosis and treatment pathway for primary care; does not address HBV |
| 31360020 | 2019 | Real-world study | J Clin Exp Hepatol | Generic pan-genotypic sofosbuvir/velpatasvir experience for chronic HCV in Myanmar; HCV-specific |
| 34092970 | 2021 | Review | World J Gastroenterol | Review of pediatric viral hepatitis management, covering both HBV and HCV therapies broadly, but does not report velpatasvir activity against HBV specifically |
| 32935438 | 2021 | Cohort study | J Viral Hepat | Simplified HCV treatment strategy in Myanmar; HBV-coinfected participants were treated concurrently with tenofovir, not velpatasvir, for their HBV infection |
| 32405174 | 2020 | Case series | J Clin Exp Hepatol | Sofosbuvir/velpatasvir experience in HCV patients with end-stage renal disease/kidney transplant; no HBV outcome reported |
Note: Across the full 20-record literature set, only one item (the 2019 case report) directly links velpatasvir to HBV, and it describes a reactivation risk rather than therapeutic benefit. The remainder either study HCV exclusively or mention HBV only in the context of co-infected populations managed with separate HBV-specific antivirals (e.g., tenofovir).
EU Market Information
Velpatasvir has no standalone EU marketing authorization on record in this dataset (0 licenses, market status: Not marketed). It is only available in the EU as part of fixed-dose combination products (e.g., sofosbuvir/velpatasvir, marketed as Epclusa, and sofosbuvir/velpatasvir/voxilaprevir, marketed as Vosevi), which fall outside the scope of the regulatory data captured for this candidate.
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Velpatasvir’s mechanism (HCV NS5A inhibition) has no known homologous target in HBV, and virtually all collected trial and literature evidence for this pairing reflects HCV treatment studies or HCV/HBV co-infection contexts rather than genuine anti-HBV activity — the one direct HBV-related report describes a reactivation risk, not efficacy. This pattern indicates the TxGNN signal is likely driven by shared clinical co-occurrence rather than true biological plausibility.
To proceed, the following is needed:
- Regulatory label data (warnings/contraindications) from the relevant national/EU authority — currently a blocking data gap that prevents any initial safety assessment (S1)
- Confirmed mechanism-of-action documentation from DrugBank or equivalent source
- Dedicated in vitro or in vivo studies testing velpatasvir activity against HBV replication, to distinguish true mechanistic relevance from co-infection-context contamination in the evidence base
- If any such preclinical signal emerges, monitoring of HBV reactivation risk should be a specific safety focus, given the existing case-report signal
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.