Pibrentasvir
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Pibrentasvir: From Hepatitis C Virus Infection to Hepatitis B Virus Infection
One-Sentence Summary
Pibrentasvir is an NS5A inhibitor marketed only as part of the fixed-dose combination glecaprevir/pibrentasvir (Mavyret), approved for chronic Hepatitis C virus (HCV) infection. The TxGNN model predicts a possible effect on Hepatitis B virus (HBV) infection (score 99.84%), but on review the supporting 14 clinical trials and 20 publications all study glecaprevir/pibrentasvir for HCV — none test the drug against HBV, and the evidence reviewers flagged this as a likely graph co-occurrence artifact rather than a genuine pharmacological signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic Hepatitis C virus (HCV) infection, as a component of the glecaprevir/pibrentasvir fixed-dose combination (Mavyret) |
| Predicted New Indication | Hepatitis B Virus Infection |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L5 (model prediction only, no direct supporting studies) |
| Germany Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
A formal, sourced mechanism-of-action record for pibrentasvir is not currently available in this evidence pack (data gap, high severity — see DG002). Based on information embedded in the trial and literature evidence, however, pibrentasvir is known to be an HCV NS5A protein dimerization inhibitor, always co-administered with glecaprevir (an NS3/4A protease inhibitor) as Mavyret. Its efficacy is well established for chronic HCV genotypes 1–6.
HCV (Flaviviridae, Hepacivirus) and HBV (Hepadnaviridae) are taxonomically and structurally unrelated viruses. HBV has no NS5A homolog, so there is no known target-level basis for cross-activity. Reviewing the 14 clinical trials and 20 publications linked to this prediction, all of them evaluate glecaprevir/pibrentasvir efficacy, safety, or pharmacokinetics in HCV-infected patients; a few touch on HBV only tangentially (e.g., HBV vaccination after HCV cure, or HBV/HCV co-screening populations), never as a treatment endpoint for HBV itself.
This pattern is consistent with the reviewers' assessment: the high TxGNN score likely reflects a graph co-occurrence signal (HBV and HCV are frequently screened, studied, and discussed together in the same clinical and literature contexts) rather than a real pharmacological relationship. Mechanistically, there is currently no basis to expect pibrentasvir to have anti-HBV activity.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03823911 | Phase 4 | Completed | 87 | Cardiovascular risk outcomes after HCV eradication in HIV/HCV co-infected patients; not an HBV study. |
| NCT03219216 | Phase 3 | Completed | 100 | Efficacy/safety of GLE/PIB in treatment-naïve Brazilian adults with chronic HCV GT1–6; no HBV endpoint. |
| NCT02640482 | Phase 3 | Completed | 304 | ENDURANCE-2: GLE/PIB efficacy/safety in HCV genotype 2 infection; graded C — not relevant to HBV. |
| NCT02243293 | Phase 2/3 | Completed | 694 | SURVEYOR-II: GLE/PIB ± ribavirin in chronic HCV GT2–6; graded C — HBV co-infection possibly excluded/screened, not treated. |
| NCT02243280 | Phase 2 | Completed | 174 | SURVEYOR-I: GLE/PIB ± ribavirin in HCV GT1,4,5,6 infection. |
| NCT01995071 | Phase 2 | Completed | 89 | Dose-ranging safety/antiviral activity of GLE/PIB components in HCV GT1 infection. |
| NCT02441283 | Phase 2/3 | Completed | 384 | Long-term follow-up of DAA resistance durability in prior HCV GLE/PIB trial participants. |
| NCT02296905 | Phase 1 | Completed | 24 | Pharmacokinetics/safety of GLE/PIB in hepatic impairment (not HBV-specific). |
| NCT03092375 | Phase 3 | Completed | 177 | G/P ± ribavirin in GT1 HCV patients previously treated with an NS5A inhibitor + sofosbuvir. |
| NCT02640157 | Phase 3 | Completed | 506 | ENDURANCE-3: GLE/PIB vs. sofosbuvir+daclatasvir in HCV genotype 3 infection. |
Note: All 14 trials associated with this prediction study glecaprevir/pibrentasvir for HCV treatment. None enroll patients for an HBV treatment endpoint.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29485084 | 2018 | Review | Lancet Infect Dis | Discusses HBV vaccination after HCV treatment — a care-pathway topic, not anti-HBV drug efficacy. |
| 34298832 | 2021 | Review | Cancers | Reviews hepatocellular carcinoma risk in chronic kidney disease; mentions viral hepatitis as a risk factor context only. |
| 31981264 | 2020 | Cohort | J Viral Hepat | Real-world GLE/PIB effectiveness/safety in HCV patients with severe renal impairment in Taiwan. |
| 30982721 | 2019 | Review | Lancet Gastroenterol Hepatol | Overview of HCV infection management in children/adolescents. |
| 30964552 | 2019 | — | Hepatology | Characterizes HCV protease-inhibitor resistance-associated substitutions. |
| 34092970 | 2021 | Review | World J Gastroenterol | Reviews management advances for pediatric HBV and HCV, discussing both viruses separately (no combined therapy claim). |
| 35579223 | 2022 | — | Eur J Gen Pract | Practical guide to chronic HCV diagnosis and treatment for primary care. |
| 31041789 | 2019 | — | Semin Liver Dis | Reviews retreatment strategies for HCV patients who failed prior DAA regimens. |
| 35431505 | 2022 | — | World J Gastroenterol | Real-world DAA effectiveness in HIV/HCV genotype 6 co-infected patients. |
| 40414600 | 2025 | — | Ann Hepatol | Cross-country comparison of HBV and HCV antiviral drug pricing (health-economics topic, not efficacy data). |
Note: None of the reviewed literature reports pibrentasvir being tested for, or effective against, HBV.
Germany Market Information
Pibrentasvir is currently not marketed in Germany, and no BfArM authorization records exist for this evidence pack (0 licenses on file).
Safety Considerations
Please refer to the package insert for safety information.
(Note: A blocking data gap exists — official warnings/contraindications from the label are not yet available, which prevents a full S1 safety assessment. See remediation plan below.)
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high, but every piece of supporting evidence (14 trials, 20 publications) concerns glecaprevir/pibrentasvir's established use against HCV, not HBV. There is no mechanistic basis (HBV lacks an NS5A homolog) and no direct experimental or clinical data suggesting anti-HBV activity. The evidence level is L5 — model prediction only — and the drug is unlicensed in this market. The same pattern holds across this drug's other top-10 TxGNN predictions (HIV, HEV, HAV, Omsk hemorrhagic fever, Kyasanur forest disease, and several animal/rare-disease indications), which the evidence reviewers likewise flagged as graph co-occurrence noise or taxonomic-homology artifacts with no supporting data. This candidate should not advance beyond Hold without new primary evidence.
To proceed, the following is needed:
- Confirmed mechanism-of-action documentation (DG002 remediation via DrugBank API)
- TFDA/BfArM label warnings and contraindications (DG001 — blocking, required before any S1 safety review)
- In vitro anti-HBV screening data for pibrentasvir, if repurposing interest continues
- Reassessment against future TxGNN model versions with cleaner disease-similarity signal, given the apparent HCV/HBV co-occurrence bias observed here
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.