Ledipasvir

Evidence Level: L2

Predicted Indications: 10

Ledipasvir

Pharmacist Assessment Report

Ledipasvir: From Chronic Hepatitis C to Hepatitis B Virus Infection

One-Sentence Summary

Ledipasvir is an HCV NS5A inhibitor, used in fixed-dose combination with sofosbuvir for chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for hepatitis B virus infection, but direct support is thin: one single-arm Phase 2 study (21 patients) tests the indication, and the remaining trials and publications are mostly about HCV treatment or HBV reactivation during HCV therapy. The mechanistic basis for an anti-HBV effect is weak, so this should be treated as a research question rather than a ready candidate.

Quick Overview

Item	Content
Original Indication	Chronic hepatitis C virus infection (hepatitis C virus infection)
Predicted New Indication	Hepatitis B virus infection
TxGNN Prediction Score	0.9991
Evidence Level	L2 (by the scoring rules; see the note below)
India Market Status	Listed in a compiled Indian medicine price dataset (14 of 14) – CDSCO approval status is not included in this data
Number of Listed Products	14 (valid: 14)
Recommended Decision	Hold

Note on evidence level: The only completed Phase 2/3 study (NCT02555943, n=23) is in HCV/HBV co-infection and measures HCV cure as its primary endpoint. The only study that directly tests HBV is a single-arm Phase 2 pilot. The strict L2 label therefore overstates the strength of the evidence for HBV efficacy.

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available. Based on known information, ledipasvir is an NS5A inhibitor used with the NRTI sofosbuvir, and its efficacy in hepatitis C has been established.

The prediction is difficult to support mechanistically. HBV is a DNA hepadnavirus with a different replication machinery from HCV, and ledipasvir has no established anti-HBV activity. The high TxGNN score most likely reflects network proximity to HCV (both are hepatotropic viruses) rather than a real shared target.

Some clinical signals exist. A Phase 2 open-label study of ledipasvir/sofosbuvir for 12 weeks in HBV mono-infected subjects (NCT03312023, published as PMID 36045503) was built on retrospective observations of a modest HBsAg reduction in HBV/HCV co-infected patients. It is a small, single-arm study (n=21) and does not establish efficacy. Studies in co-infected patients mainly show that HCV is cleared, and HBV reactivation during DAA therapy is a safety concern rather than a therapeutic signal.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03312023	Phase 2	Completed	21	Open-label ledipasvir/sofosbuvir for 12 weeks in HBV-infected subjects; the study directly tests the indication, with HBsAg and HBV DNA decline as endpoints
NCT02555943	Phase 2/3	Completed	23	Direct-acting antivirals in HCV/HBV co-infection; studies HBV reactivation during anti-HCV treatment, with HCV cure as the primary endpoint
NCT02836925	Phase 2	Completed	40	Interferon-free ledipasvir or velpatasvir regimens in HCV-associated indolent B-cell lymphoma; HBV relevance is indirect
NCT03261349	Phase 2	Unknown	21	Ledipasvir/sofosbuvir in HCV-associated indolent B-cell non-Hodgkin lymphoma; link to HBV is unconfirmed
NCT02768961	Phase 4	Completed	64	HCV screening and elimination program in prisons, which also screens for HBV and HIV; not an anti-HBV efficacy test

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, with HBsAg and HBV DNA decline at Week 12 as endpoints
29174546	2018	Prospective study	Gastroenterology	Ledipasvir/sofosbuvir for HCV in HBV co-infected patients, assessing HBV reactivation risk
34864948	2022	Cohort	Clin Infect Dis	HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up in Taiwanese HCV/HBV co-infected patients
27367295	2016	Pilot study	Antivir Ther	Ledipasvir/sofosbuvir suppresses HCV in patients co-infected with HBV
33523503	2021	Cohort	J Viral Hepat	HBV reactivation in cancer patients receiving DAAs for HCV
29334502	2018	Cohort	J Clin Gastroenterol	Risk of HBV reactivation among patients treated with ledipasvir-sofosbuvir for HCV
28585404	2017	Prospective cohort	Hepatol Res	Frequency of and factors associated with HBV reactivation during all-oral DAA therapy in a Japanese cohort
26967675	2016	Review	J Clin Virol	HBV reactivation as a further challenge in DAA treatment of HCV

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
209193	Sofokem L 90mg/400mg Tablet (Alkem Laboratories)	Strip of 28 tablets	Not specified
186367	Reclaim-L Tablet (Lupin)	Bottle of 28 tablets	Not specified
104176	Hepcvir L 90mg/400mg Tablet (Cipla)	Strip of 28 tablets	Not specified
104373	Hepcinat-LP Tablet (Natco Pharma)	Strip of 28 tablets	Not specified
125977	Ledihep Tablet (Zydus Cadila)	Strip of 28 tablets	Not specified

Fourteen valid registrations are listed in total; all are oral tablets. The first five are shown here.

Review correction (2026-11-06): Originally stated: “Fourteen valid single-ingredient registrations are listed in total; all are oral tablets.” Removed: it described the products as single-ingredient or combination products in a way that did not match the Indian medicine data (the Indian Medicine Dataset as of 2026-11-06). Source: Indian Medicine Dataset.

Safety Considerations

Drug Interactions: 65 interactions were identified in total. The ones listed below are mostly Moderate, and the main ones fall into these groups:
- Antacids (aluminum hydroxide, calcium carbonate, magaldrate, magnesium carbonate, magnesium hydroxide, magnesium oxide)
- Acid suppressants: H2 blockers (cimetidine, famotidine, nizatidine) and proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole)
- Others: eliglustat, linagliptin, loperamide and naldemedine (all Moderate), and fidaxomicin and naloxegol (both Minor)
HBV reactivation: Published cohorts and case reports describe HBV reactivation in HBV/HCV co-infected or previously HBV-exposed patients treated with ledipasvir/sofosbuvir. This is the main safety issue for any use in HBV-infected patients.

Please refer to the package insert for warnings and contraindications, as this information was not available in the data compiled for this report.

Conclusion and Next Steps

Decision: Hold

Rationale: Ledipasvir has no established anti-HBV mechanism, and the direct evidence is a single 21-patient, single-arm Phase 2 pilot. The other studies mainly show HCV cure or HBV reactivation risk. The high TxGNN score likely reflects network proximity to HCV rather than real HBV activity. The product is widely marketed in India, which makes access easy but does not strengthen the case for efficacy.

To proceed, the following is needed:

Detailed mechanism of action data and in vitro anti-HBV activity data for ledipasvir alone
Full results of the HBV mono-infection pilot (PMID 36045503), followed by a controlled study with HBsAg and HBV DNA endpoints
Package insert warnings and contraindications from the Indian regulatory sources
An HBV reactivation monitoring plan for any HBV-positive population, and a review of interactions with acid-suppressing drugs

Other predicted indications (for reference): Hepatitis E virus infection (L4, Hold) rests on a single case report of ribavirin-refractory infection treated with ledipasvir/sofosbuvir plus ribavirin; any effect is more plausibly due to sofosbuvir. Chronic hepatitis B virus infection (L3) has the same limitations as the lead indication. The remaining predictions (hepatitis A, Omsk hemorrhagic fever, Kyasanur forest disease, HIV infection, and animal or veterinary viral diseases) are model-only (L5) or reflect HCV treatment in other populations, and should be held.

Review Log

Below is the review log for this page: statements checked against official Indian medicine data (the Indian Medicine Dataset used by this site). Corrections are limited to basic factual statements; model predictions, evidence levels, and conclusions were not rewritten.

Review date	Item	Action	Source
2026-11-06	Removed: “single-ingredient”	Corrected	Indian Medicine Dataset

Disclaimer

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