Delamanid
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Delamanid: From Multidrug-Resistant Tuberculosis to Bovine Tuberculosis
One-Sentence Summary
Delamanid is a nitroimidazole antimycobacterial originally used for multidrug-resistant pulmonary tuberculosis (MDR-TB). The TxGNN model predicts it may also be effective for Bovine Tuberculosis (zoonotic Mycobacterium bovis infection), but this direction is currently supported only by a prediction score and 1 indirect publication (a pathogen genomics study, not a drug-efficacy study) — no clinical trials exist for this specific pairing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Multidrug-resistant tuberculosis (MDR-TB) — noted in evidence-pack rationale; no EU/TFDA label text available in this pack |
| Predicted New Indication | Tuberculosis, Bovine |
| TxGNN Prediction Score | 99.91% |
| Evidence Level | L4 |
| EU Market Status | Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data (original_moa) is not available for delamanid in this evidence pack. Based on the repurposing rationale associated with this prediction, delamanid is a nitro-dihydro-imidazooxazole prodrug that is activated by the mycobacterial Ddn nitroreductase system and subsequently inhibits mycolic acid (cell wall) synthesis — a mechanism it shares with its approved indication of MDR pulmonary tuberculosis caused by Mycobacterium tuberculosis.
Mycobacterium bovis, the causative agent of bovine tuberculosis, belongs to the same Mycobacterium tuberculosis complex and shares the mycolic acid synthesis pathway and Ddn activation system. This provides a plausible mechanistic bridge: in theory, delamanid should retain activity against M. bovis.
However, this extrapolation carries important caveats noted directly in the evidence pack: M. bovis has intrinsic resistance to pyrazinamide, and drug-susceptibility data for other anti-TB agents (including delamanid specifically) against M. bovis is scarce. Zoonotic TB is effectively an orphan indication here, and no delamanid-specific in vitro or clinical susceptibility data currently exists.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39487429 | 2024 | Cohort/Epidemiology | BMC Genomics | Whole-genome sequencing study characterizing genetic diversity and drug-resistance patterns of M. bovis isolates from zoonotic human TB cases; this is a pathogen genomics study and does not evaluate delamanid efficacy directly |
EU Market Information
Delamanid currently has no EU marketing authorizations recorded in this evidence pack (0 licenses; market status: Not Marketed).
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The only supporting evidence for this specific prediction is the TxGNN score plus a single pathogen-genomics publication that does not test delamanid; there are no clinical trials, no drug-specific susceptibility data against M. bovis, and no EU marketing authorization to anchor a safety/regulatory pathway. This falls short of the threshold to proceed even under guardrails.
To proceed, the following is needed:
- TFDA/EMA product label (SmPC) with warnings and contraindications — currently a blocking data gap (DG001) that prevents any S1 safety screening
- Confirmed mechanism of action via DrugBank API (DG002)
- In vitro/preclinical susceptibility data of delamanid specifically against M. bovis
- Any clinical or case-series evidence of delamanid use in human zoonotic/bovine TB
Note: Within this same evidence pack, a related candidate indication — inactive tuberculosis (latent/non-active TB, rank 3) — has substantially stronger evidence (L2, including an ongoing Phase 3 trial, NCT03568383, PHOENIx MDR-TB, n=5,832, and 20 supporting publications). If the goal is to identify the most defensible repurposing direction for delamanid, that candidate warrants prioritized evaluation over bovine tuberculosis.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.