Peginterferon Alfa-2A
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Peginterferon Alfa-2A
- Peginterferon Alfa-2a: From Chronic Hepatitis C and B to Hepatitis B Virus Infection
Peginterferon Alfa-2a: From Chronic Hepatitis C and B to Hepatitis B Virus Infection
One-Sentence Summary
Peginterferon alfa-2a was originally used to treat chronic hepatitis C and chronic hepatitis B virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, which is in fact already one of its established uses, so this is an on-label use rather than true repurposing. Currently 19 clinical trials and 20 publications support this direction, including several randomized controlled trials and meta-analyses.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection; chronic hepatitis B virus infection (US label indication text is not available) |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 99.94% |
| Evidence Level | L1 |
| US Market Status | Cancelled only (no currently valid license) |
| Number of NDAs | 1 (BLA103964, cancelled) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, peginterferon alfa-2a is a pegylated form of interferon alfa. It acts through the interferon-alpha receptor and induces interferon-stimulated genes, giving it both direct antiviral and immunomodulatory effects. These effects are thought to support control of HBV replication and loss of the surface antigen (HBsAg).
Chronic hepatitis B is already listed among the drug’s original indications, so the prediction mostly confirms existing use. The many HBV trials and publications on file are consistent with this.
The main caution is regulatory. The only US license on record (Pegasys, BLA103964) is cancelled, so product availability and local regulatory status must be confirmed before any use.
Clinical Trial Evidence
The 10 most relevant of the 19 trials registered for this indication are listed below. Trials are ordered by relevance grade, then enrollment.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02604823 | Phase 4 | Completed | 307 | Efficacy and safety of peginterferon alfa-2a in HBeAg-positive chronic hepatitis B, with 48 weeks of treatment and 24 weeks of follow-up |
| NCT00661076 | Phase 3 | Completed | 10 | Randomized comparison of Pegasys plus adefovir versus Pegasys alone in HBeAg-negative disease; direct evidence, but very small |
| NCT00614471 | Phase 4 | Completed | 219 | Randomized study of Pegasys plus entecavir (concurrent or sequential) in treatment-naive HBeAg-positive patients |
| NCT02474316 | Phase 4 | Unknown | 366 | Randomized study of switching NA-treated HBeAg-positive patients to peginterferon plus NA for 48 weeks |
| NCT02560649 | Phase 4 | Unknown | 324 | Response-guided therapy adding peginterferon in NUC-experienced patients to improve HBsAg clearance |
| NCT03181113 | N/A | Completed | 473 | Long-term follow-up cohort of HBeAg-positive patients previously treated with peginterferon |
| NCT02097004 | Phase 4 | Completed | 111 | Therapeutic vaccination plus peginterferon for HBsAg seroclearance after entecavir response |
| NCT01906580 | Phase 4 | Unknown | 105 | Combination versus sequential peginterferon and entecavir in HBeAg-positive patients |
| NCT03084250 | Phase 4 | Unknown | 150 | Randomized study of adding peginterferon to NA in high-HCC-risk patients with cirrhosis |
| NCT02570191 | Phase 4 | Completed | 60 | Single-arm, open-label study of efficacy and safety in HBeAg-negative chronic hepatitis B |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15987917 | 2005 | RCT | N Engl J Med | Peginterferon alfa-2a with or without lamivudine compared with lamivudine alone in HBeAg-positive chronic hepatitis B |
| 30549279 | 2019 | RCT | Hepatology | Entecavir plus peginterferon alfa-2a in adults with HBeAg-positive immune-tolerant chronic HBV |
| 26299874 | 2016 | Meta-analysis | Clin Res Hepatol Gastroenterol | Extended versus standard 48-week peginterferon alfa-2a duration in chronic hepatitis B |
| 30865588 | 2019 | Meta-analysis | Antivir Ther | Individual-participant-data analysis to define treatment stopping rules for peginterferon alfa-2a |
| 33720089 | 2021 | Randomized controlled study | J Pediatr Gastroenterol Nutr | Peginterferon alfa-2a plus lamivudine or entecavir in children with immune-tolerant CHB |
| 30318613 | 2019 | Clinical trial | Hepatology | Entecavir plus peginterferon in children with HBeAg-positive immune-tolerant CHB |
| 26700861 | 2015 | Randomized trial | Virol J | Long-term effects of peginterferon alfa-2a in Japanese patients with chronic HBV |
| 32548156 | 2020 | Cohort | World J Clin Cases | Cytokines predict virological response in patients on peginterferon alfa-2a |
| 41086952 | 2025 | Cohort | Antiviral Res | Baseline viral quasispecies features correlate with HBsAg seroconversion in children |
| 19084016 | 2009 | Clinical trial | Gastroenterology | Peginterferon alfa-2a plus ribavirin in dual HBV/HCV infection |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| BLA103964 (cancelled) | Pegasys | Injection, solution | Indication text not available |
Safety Considerations
- Drug Interactions: 100 interacting drugs were identified in the interaction database. The first 20 returned included these notable ones:
- Major: bupropion, deferiprone, iopamidol, iohexol, samarium (153Sm) lexidronam, eltrombopag
- Moderate: metronidazole, tinidazole, naltrexone, rosuvastatin, simvastatin, warfarin, dicoumarol, chloroquine, pegvaliase, palifermin, strontium chloride Sr-89, and several bowel-preparation agents (picosulfuric acid, polyethylene glycol with electrolytes, sodium sulfate)
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Peginterferon alfa-2a is an established therapy for chronic hepatitis B, with supporting RCTs, meta-analyses, and many Phase 3/4 trials. The guardrail is that the only US license is cancelled, and label-based safety data have not yet been reviewed.
To proceed, the following is needed:
- Confirm product availability and current regulatory status, since the only US license is cancelled
- Obtain and review the package insert for warnings and contraindications (a blocking gap for safety screening)
- Obtain detailed mechanism of action data
- Create an interaction management plan for the major interactions listed above
Other predicted indications: The remaining nine predictions are not supported by evidence and should not advance.
- Hepatitis E virus infection (L4, Research Question): the listed trials are all HBV studies, so only indirect evidence exists.
- Hepatitis A virus infection, viral hepatitis in animals, Omsk hemorrhagic fever, Kyasanur forest disease, heart neoplasm, heart valve disease, and congenital ventricular septum anomaly (L5, Hold): prediction only, with no relevant human evidence.
- Heart conduction disease (L5, Hold): interferon therapy has reported cardiac adverse effects such as arrhythmia, which argues against use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.