Sofosbuvir
| Evidence Level: L3 | Predicted Indications: 8 |
Table of Contents
Sofosbuvir: From Chronic Hepatitis C to Hepatitis B Virus Infection
One-Sentence Summary
Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase, originally used to treat chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, but the supporting studies are mostly HCV/HBV co-infection trials (11 clinical trials and 20 publications matched), and they mainly describe HBV reactivation and monitoring rather than HBV treatment. This prediction should be treated as a research question, not a treatment claim.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 0.9977 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Note: The Indian licence records compiled for this report have no approved-indication text, so the original indication is not stated here.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, sofosbuvir is a prodrug whose active triphosphate form inhibits the HCV NS5B RNA-dependent RNA polymerase. Its efficacy in hepatitis C is well established.
The mechanistic link to hepatitis B is weak. HBV is a DNA virus that replicates through a reverse transcriptase, so direct antiviral activity from sofosbuvir is implausible. The high TxGNN score most likely reflects the shared hepatitis and co-infection context rather than a true mechanism.
The clinically relevant observations are about co-infection: HBV reactivation and HBV-DNA/HBsAg kinetics during sofosbuvir-based HCV therapy. One small Phase 2 pilot of ledipasvir/sofosbuvir in HBV-infected subjects (published 2023) explored a modest HBsAg reduction, but it was single-arm and small.
Other predicted indications in the analysis, such as hepatitis E, are mechanistically more plausible because HEV is an RNA virus. That evidence is still limited and inconsistent (see the conclusion).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03312023 | Phase 2 | Completed | 21 | Ledipasvir/sofosbuvir for 12 weeks in HBV infection; directly relevant but single-arm, small, and likely co-infected population |
| NCT02555943 | Phase 2/3 | Completed | 23 | Anti-HCV direct-acting antivirals in HCV/HBV co-infection; studies HBV reactivation, not HBV efficacy |
| NCT04997564 | Phase 4 | Unknown | 120 | SOF/VEL with prophylactic TAF in HCV/HBV co-infection; a safety-management design, not evidence of sofosbuvir activity against HBV |
| NCT03186313 | Phase 3 | Completed | 72 | Fixed-dose sofosbuvir/daclatasvir (± ribavirin) in genotype 4 HCV; HBV-specific benefit uncertain |
| NCT02483156 | Phase 2/3 | Completed | 80 | Sofosbuvir plus ribavirin in genotype 4 HCV; HBV relevance limited to co-infection |
| NCT03549312 | Phase 4 | Unknown | 25 | HIV/HCV switch study; the HBV-active component is TAF, not sofosbuvir |
| NCT03261349 | Phase 2 | Unknown | 21 | Ledipasvir/sofosbuvir in HCV-associated B-cell lymphoma; unclear HBV relevance |
| NCT03579576 | N/A | Completed | 803 | Simplified HCV treatment model in Myanmar; programmatic, no HBV efficacy signal |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36045503 | 2023 | Phase 2 open-label trial | J Med Virol | Ledipasvir/sofosbuvir for 12 weeks in HBV mono-infection, testing HBsAg and HBV-DNA decline |
| 42558970 | 2026 | Clinical study | J Clin Transl Hepatol | SOF/VEL with TAF pre-treatment in HBV/HCV co-infection, assessing HBV reactivation |
| 35268497 | 2022 | Cohort | J Clin Med | HBV-DNA and HBsAg kinetics in HCV co-infected patients during DAA therapy |
| 42145438 | 2026 | Comparative study | Bioinformation | Tenofovir/entecavir for HBV compared with sofosbuvir-based or glecaprevir/pibrentasvir regimens for HCV; the drugs treat different viruses |
| 26967675 | 2016 | Review | J Clin Virol | HBV reactivation during DAA treatment of HCV is a further challenge |
| 25027705 | 2014 | Review | Minerva Gastroenterol Dietol | Antiviral medications for hepatitis B and C and their effects on kidney function |
| 33523503 | 2021 | Prospective observational | J Viral Hepat | HBV reactivation in cancer patients receiving DAAs for HCV |
| 31542053 | 2019 | Case report | J Med Case Rep | HBV reactivation with an immune-escape mutant during sofosbuvir/velpatasvir treatment |
India Market Information
Sofosbuvir has 20 valid single-ingredient registrations in India. Approved-indication text is not recorded for these licences. Five main registrations:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 200970 | Sovaldi 400mg Tablet (Mylan) | Bottle of 28 tablets | Not recorded |
| 202464 | Sofocure Tablet (Emcure) | Strip of 10 tablets | Not recorded |
| 103807 | Hepcvel Tablet (Cipla) | Bottle of 28 tablets | Not recorded |
| 104281 | Hepcinat Tablet (Natco) | Strip of 28 tablets | Not recorded |
| 185663 | Resof 400mg Tablet (Dr Reddy’s) | Strip of 28 tablets | Not recorded |
All dosage forms are oral tablets.
Safety Considerations
- Drug Interactions (8 interactions found):
- Major: apalutamide, enzalutamide, lorlatinib
- Moderate: fostamatinib, warfarin, dicoumarol, encorafenib
- Minor: cyclosporine
- HBV reactivation: Multiple reports and studies describe HBV reactivation in HBV/HCV co-infected patients treated with sofosbuvir-based regimens. HBV screening and prophylaxis or monitoring (e.g., with TAF) are the clinically relevant issue.
Please refer to the package insert for further safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Sofosbuvir targets an RNA polymerase and has no plausible direct activity against the DNA virus HBV. The available trials and papers mainly concern HCV/HBV co-infection, where the findings relate to HBV reactivation risk rather than HBV treatment. The only directly relevant trial is a small, single-arm Phase 2 pilot of ledipasvir/sofosbuvir, and its population was likely co-infected.
Among the other predictions, hepatitis E virus is more plausible mechanistically (in vitro inhibition, additive effect with ribavirin), but a small Phase 2 pilot (n=10) and case reports show no sustained virological response, with resistance-associated variants emerging. Hepatitis A, Kyasanur forest disease, Omsk hemorrhagic fever and the “animal viral hepatitis” category rest on in vitro or biochemical data or none at all. The HIV prediction reflects HCV cure in HIV-coinfected patients, not HIV activity.
To proceed, the following is needed:
- Mechanism of action data from DrugBank
- Package insert warnings and contraindications from the Indian regulatory source, which is a blocking gap for safety screening
- Controlled studies in HBV mono-infected patients with HBV-specific endpoints (HBsAg, HBV-DNA)
- A HBV screening and reactivation monitoring plan for any HCV/HBV co-infected patients
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.