Daclatasvir
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Daclatasvir
- Pharmacist Assessment Report
- Daclatasvir: From Chronic Hepatitis C Virus Infection to Hepatitis B Virus Infection
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Daclatasvir: From Chronic Hepatitis C Virus Infection to Hepatitis B Virus Infection
One-Sentence Summary
Daclatasvir is an NS5A inhibitor originally used to treat chronic hepatitis C virus (HCV) infection. The TxGNN model predicts it may be effective for Hepatitis B Virus Infection, but the supporting evidence is weak: the 4 clinical trials and 20 publications retrieved all concern HCV treatment (including in HBV co-infected patients) and show no anti-HBV efficacy. Several reports describe HBV reactivation during daclatasvir-based therapy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection |
| Predicted New Indication | Hepatitis B virus infection |
| TxGNN Prediction Score | 0.9980 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (17 of 17) – CDSCO approval status is not included in this data |
| Number of Listed Products | 17 (valid: 17) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, daclatasvir is a direct-acting antiviral that targets the HCV NS5A protein, part of the replication complex. It is used with other agents such as sofosbuvir for HCV, and its efficacy there is well established.
The link to HBV is weak. HBV and HCV are both hepatotropic viruses. But HBV is a DNA virus that replicates through reverse transcription, and it has no NS5A equivalent. Daclatasvir has no established anti-HBV activity. The very high score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
The clinical literature points the other way. Case reports and cohorts describe HBV reactivation or acute hepatitis B in HBV/HCV co-infected patients during daclatasvir-based therapy. This is a safety signal, not a therapeutic one.
The other top predictions (HIV, hepatitis E, hepatitis A, Omsk hemorrhagic fever, Kyasanur forest disease, and animal or neurodevelopmental conditions) rest on even less evidence. Their scores come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. They are not pursued here.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02555943 | Phase 2/3 | Completed | 23 | Direct-acting antivirals in HCV/HBV co-infected patients. Examines HBV reactivation during anti-HCV treatment, not HBV efficacy. |
| NCT03186313 | Phase 3 | Completed | 72 | Fixed-dose sofosbuvir + daclatasvir (± ribavirin) in Egyptian adults with genotype 4 HCV. HBV is not the therapeutic target. |
| NCT01795911 | Phase 2 | Completed | 165 | Peginterferon lambda with ribavirin and daclatasvir in genotype 1 HCV. HBV relevance is indirect at most. |
| NCT01425970 | Phase 2 | Terminated | 210 | INX-08189 with daclatasvir and/or ribavirin in HCV genotype 2/3. No HBV efficacy data. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31722032 | 2020 | Cohort | Trans R Soc Trop Med Hyg | Sofosbuvir/daclatasvir therapy in chronic HCV and HCV/HBV co-infected patients in Egypt |
| 29194858 | 2018 | Cohort-type study | J Viral Hepat | Low incidence of HBV reactivation and subsequent hepatitis in 25 HBV co-infected patients and 765 patients with resolved HBV during DAA therapy |
| 26297529 | 2016 | Cohort | Hepatol Res | HBV reactivation during daclatasvir + asunaprevir in an HBV/HCV co-infected patient |
| 27329484 | 2016 | Case report | Clin J Gastroenterol | Acute hepatitis B after daclatasvir + asunaprevir in an HCV patient. Unclear whether reactivation or self-limited infection. |
| 24631495 | 2014 | Review | Gastroenterology | Overview of new HCV therapies and strategies |
| 23567084 | 2013 | Review | J Hepatol | NS5A inhibitors in HCV treatment |
| 26904396 | 2016 | Review | Acta Pharm Sin B | Direct anti-HCV agents. Notes that, unlike HBV, HCV is curable. |
| 36838792 | 2023 | In silico | Molecules | Virtual screening of HBV pre-genomic RNA as a target. Computational and not specific to daclatasvir. |
India Market Information
Daclatasvir is marketed in India as a single-agent oral tablet, with 17 valid registrations from many manufacturers. The registration records include no approved-indication text. A selection of five is shown below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Registration No. 64547 | Daclacure 60mg Tablet (Emcure) | Strip of 28 tablets | Not specified in the registration record |
| Registration No. 62170 | Dalsiclear 60 Tablet (Abbott) | Bottle of 28 tablets | Not specified in the registration record |
| Registration No. 67502 | Daclafab 60mg Tablet (Sun Pharma) | Strip of 28 tablets | Not specified in the registration record |
| Registration No. 104213 | Hepcdac 60mg Tablet (Cipla) | Strip of 28 tablets | Not specified in the registration record |
| Registration No. 105006 | Hepcfix 60mg Tablet (Dr Reddy’s) | Strip of 28 tablets | Not specified in the registration record |
Safety Considerations
- Drug Interactions: 89 interactions are recorded. Examples of major-level interactions include dexamethasone, clarithromycin, eluxadoline and cobicistat. Moderate-level examples include metformin, loperamide, aprepitant, rosuvastatin, simvastatin and apixaban.
- HBV reactivation: The literature describes HBV reactivation and acute hepatitis B in HBV/HCV co-infected patients during daclatasvir-based therapy. HBV screening and monitoring are important in this setting.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: Daclatasvir has no established anti-HBV mechanism. The available trials and publications all concern HCV treatment, and the HBV-related reports raise a safety concern (reactivation) rather than showing efficacy. The high TxGNN score likely reflects network proximity between viral hepatitis nodes.
To proceed, the following is needed:
- In vitro evidence of anti-HBV activity (for example, HBV replication assays) before any clinical consideration
- Detailed mechanism of action data
- Package insert warnings and contraindications from the India regulatory source
- A clear HBV reactivation risk-management plan for any co-infected population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.