Velpatasvir

證據等級: L5

預測適應症: 10 個

Velpatasvir: From Chronic Hepatitis C to Hepatitis B Virus Infection

One-Sentence Summary

Velpatasvir is an NS5A-inhibitor antiviral used in fixed-dose combination products (e.g., sofosbuvir/velpatasvir) for chronic hepatitis C. TxGNN predicts it may also be effective against Hepatitis B Virus Infection (score 99.87%), but of the 26 clinical trials and 20 publications retrieved for this pairing, only one trial and one case report actually reference HBV — and neither shows an antiviral effect of velpatasvir against HBV itself.

Quick Overview

Item	Content
Original Indication	Chronic hepatitis C (as part of fixed-dose combinations such as sofosbuvir/velpatasvir) — no formal indication record found in this evidence pack
Predicted New Indication	Hepatitis B Virus Infection
TxGNN Prediction Score	99.87%
Evidence Level	L4
Finland Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for velpatasvir is officially flagged as a data gap in this evidence pack. Based on the trial and literature context that is present, velpatasvir is known to act as an NS5A protein inhibitor and is used exclusively in combination antiviral regimens (with sofosbuvir, ± voxilaprevir) for chronic hepatitis C virus (HCV) infection — its "original indication" here has to be inferred from trial context rather than a confirmed regulatory record.

Hepatitis C and hepatitis B are both hepatotropic viral infections, which is likely why a knowledge-graph model such as TxGNN would place them close together (shared organ tropism, shared "viral hepatitis" phenotype, overlapping patient populations, and shared literature co-occurrence). However, the two viruses are biologically unrelated at the molecular target level: HCV is a single-stranded RNA virus (Flaviviridae) whose NS5A protein is velpatasvir's target, while HBV is a partially double-stranded DNA virus (Hepadnaviridae) that replicates via reverse transcriptase and has no NS5A homolog. There is therefore no established mechanistic basis for velpatasvir having direct anti-HBV activity.

Consistent with this, the vast majority of the 26 retrieved clinical trials and 20 publications are studies of sofosbuvir/velpatasvir (or sofosbuvir/velpatasvir/voxilaprevir) treating HCV, in some cases in patients who happen to be HCV/HBV co-infected. Only one trial (NCT04997564, TAF prophylaxis against HBV reactivation during HCV treatment) and one case report (PMID 31542053, HBV reactivation during SOF/VEL therapy for HCV) reference HBV directly — and both describe HBV as a co-infection/reactivation safety concern during HCV treatment, not as a treatment target of velpatasvir itself. This indicates the TxGNN association is very likely driven by network/phenotype proximity rather than validated pharmacology.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04997564	Phase 4	Unknown	120	Only trial in the set that directly addresses HBV: prophylactic TAF + 12-week SOF/VEL in HCV/HBV co-infected patients, to prevent HBV reactivation during HCV treatment — an HBV safety-management study, not an HBV efficacy study of velpatasvir
NCT02625909	Phase 3	Completed	222	Shortened interferon-free SOF/VEL therapy for recently acquired HCV (± HIV coinfection); graded "C" — unrelated to HBV
NCT01858766	Phase 2	Completed	379	SOF/VEL ± ribavirin efficacy/safety in treatment-naive chronic HCV (genotypes 1–6); graded "C" — unrelated to HBV
NCT06180590	N/A	Recruiting	200	Real-world Vosevi (SOF/VEL/VOX) effectiveness in DAA-failure HCV patients; graded "C" — unrelated to HBV
NCT02996682	Phase 3	Completed	102	SOF/VEL ± ribavirin in chronic HCV with decompensated cirrhosis — establishes VEL safety in advanced liver disease, no HBV endpoint
NCT02533427	Phase 1	Completed	15	Drug-interaction study of SOF/VEL/VOX with a hormonal contraceptive — pharmacokinetic, no HBV relevance
NCT03570112	N/A	Completed	40	Natural history/vertical transmission of chronic HCV in pregnancy, with postpartum SOF/VEL treatment — no HBV endpoint
NCT05016609	Phase 4	Unknown	1800	Test-and-treat HCV care models among people who inject drugs — no HBV endpoint
NCT03823911	Phase 4	Completed	87	Cardiovascular outcomes after HCV eradication in HIV/HCV patients — no HBV endpoint
NCT03086044	Phase 4	Unknown	148	Transplanting organs from HCV-positive donors to HCV-negative recipients — no HBV endpoint

Note: These trials were returned by an "HBV infection" evidence query, but essentially all of them are chronic HCV treatment/safety studies. Only NCT04997564 addresses HBV, and only as a reactivation-prevention safety measure during HCV therapy — none demonstrate antiviral efficacy of velpatasvir against HBV.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
31542053	2019	Case report	Journal of medical case reports	Only HBV-specific reference: describes HBV reactivation via a surface-antigen immune-escape mutant in an anti-HBc-positive patient during SOF/VEL treatment for HCV — an adverse-event report, not evidence of anti-HBV effect
35248213	2022	RCT	Lancet Gastroenterology & Hepatology	SOF/VEL safety/efficacy in treatment-naive HCV genotype 4 patients in Rwanda — HCV efficacy trial, no HBV endpoint
34092970	2021	Review	World Journal of Gastroenterology	Reviews pediatric HBV and HCV management, including DAAs for HCV — general context, no HBV efficacy data for velpatasvir
29369303	2018	Conference report	AIDS Reviews	Summarizes HBV/HCV burden estimates and DAA advances presented at a viral hepatitis conference — background only
40414600	2025	Cross-sectional	Annals of Hepatology	Compares global HBV and HCV drug pricing — a health-economics comparison, not clinical/efficacy evidence
41734217	2025	Retrospective	Klinicka mikrobiologie a infekcni lekarstvi	Retrospective review of antiviral treatment for chronic HBV and HCV in children in Ostrava — descriptive, not velpatasvir-specific HBV data
35579223	2022	Review	European Journal of General Practice	General-practice review of chronic HCV diagnosis and treatment — no HBV content
33217040	2021	Cohort	Journal of Gastroenterology and Hepatology	Real-world SOF/VEL ± ribavirin efficacy/safety in HCV genotype 3 — no HBV content
38910758	2024	Cross-sectional	Cureus	SOF/VEL efficacy in HCV patients with chronic kidney disease — no HBV content
31114957	2019	Review	Clinical Pharmacokinetics	PK/PD review of DAA regimens (including SOF/VEL) for HCV — no HBV content

Note: Of the 20 publications retrieved, only PMID 31542053 mentions HBV directly, and it describes a reactivation adverse event during HCV treatment rather than any therapeutic benefit of velpatasvir against HBV.

Finland Market Information

No marketing authorization was found for velpatasvir in Finland (total_licenses = 0, market status: Not marketed). No authorization number, product name, or approved-indication text is available in this evidence pack.

Safety Considerations

Please refer to the package insert for safety information. (Key warnings, contraindications, and drug-interaction data are not available in this evidence pack; DDI database query returned no results.)

Conclusion and Next Steps

Decision: Hold

Rationale: Although the TxGNN score is high (99.87%), there is no plausible mechanistic basis for velpatasvir — an HCV NS5A inhibitor — to have direct antiviral activity against HBV, a hepadnavirus with no NS5A homolog. Nearly all retrieved trials and publications are HCV treatment studies; only one trial and one case report reference HBV at all, and both describe HBV reactivation/co-infection safety management rather than therapeutic efficacy against HBV.

To proceed, the following is needed:

Confirmed mechanism-of-action data for velpatasvir (DG002) and TFDA/EU package-insert warnings and contraindications (DG001), both currently flagged as blocking data gaps
In vitro or preclinical evidence of any anti-HBV activity for velpatasvir before further evaluation is warranted
If such evidence emerges, re-score against the L1–L5 evidence framework; absent it, this candidate should not advance past S0
Disclaimer

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