Enfuvirtide
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Enfuvirtide: From HIV-1 Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Enfuvirtide is an HIV-1 fusion inhibitor peptide, originally used in combination antiretroviral therapy for HIV-1 infection in treatment-experienced patients. The TxGNN model predicts relevance to Simian Immunodeficiency Virus (SIV) infection, an experimental primate model of lentiviral disease, currently supported by 0 clinical trials and 12 publications, nearly all preclinical or animal-model studies rather than human clinical evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (combination antiretroviral therapy) |
| Predicted New Indication | Simian immunodeficiency virus (SIV) infection |
| TxGNN Prediction Score | 98.18% |
| Evidence Level | L3 |
| EU Market Status | Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack. Based on known pharmacology, Enfuvirtide is a first-in-class HIV-1 fusion inhibitor peptide that binds the HR1 region of the viral envelope glycoprotein gp41, blocking the conformational change required for fusion between the viral envelope and the host cell membrane. Its efficacy in HIV-1 infection has been established in combination regimens, and mechanistically it may extend to SIV, since SIV gp41 shares high sequence homology with HIV-1 gp41 — both viruses belong to the genus Lentivirus.
However, SIV infection is not a human disease; it is a macaque-based experimental model used to study HIV pathogenesis and to validate next-generation antiviral candidates before human trials. Nearly all of the supporting literature describes preclinical work on enfuvirtide-derived lipopeptide analogs (not enfuvirtide itself) tested in SIV-infected rhesus macaques, primarily for vaccine and drug-development research rather than for treating SIV as a clinical indication in any species with therapeutic intent.
As a result, while the TxGNN score and homology-based mechanistic rationale are reasonable at the knowledge-graph level, the practical translational value of this specific “predicted indication” is limited — it reflects research-tool usage of the mechanism rather than an actionable new clinical indication for enfuvirtide.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32404526 | 2020 | Animal/Preclinical | Journal of Virology | Lipopeptide fusion inhibitor LP-52 rapidly suppressed plasma viral load in SIVmac239-infected rhesus macaques |
| 31462566 | 2019 | In vitro/Preclinical | Journal of Virology | Membrane-anchored short-peptide fusion inhibitor fully protected target cells from HIV-1, HIV-2, and SIV infection |
| 30867304 | 2019 | In vitro/Preclinical | Journal of Virology | Cholesterol-modified enfuvirtide (T-20)-derived lipopeptides showed markedly increased and long-lasting anti-HIV/SIV activity |
| 30716118 | 2019 | Cohort/Clinical (human HIV, not SIV) | PLoS Pathogens | Low-dose lipopeptide HIV fusion inhibitor maintained long-term viral suppression as monotherapy in rhesus macaques |
| 30089693 | 2018 | In vitro/Structural | Journal of Virology | Structural characterization confirms T-20 (enfuvirtide) as the reference fusion inhibitor against HIV-1, HIV-2, and SIV, noting its low potency and low resistance barrier |
| 29899103 | 2018 | Animal/Preclinical | Journal of Virology | Novel enfuvirtide-based lipopeptides (LP-50/LP-51) showed high therapeutic efficacy in rhesus monkey HIV/SIV models |
| 27795437 | 2017 | In vitro/Preclinical | Journal of Virology | Helical short-peptide fusion inhibitor derived from enfuvirtide’s target region active against HIV-1, HIV-2, and SIV |
| 28356533 | 2017 | In vitro/Preclinical | Journal of Virology | Lipopeptide HIV-1/2 fusion inhibitor built on the enfuvirtide (T-20) scaffold shows potent in vitro, ex vivo, and in vivo antiviral activity |
| 15040537 | 2004 | In vitro | Antiviral Therapy | Susceptibility screening of anti-HIV-1 compounds (including enfuvirtide-class agents) against HIV-2, SIV, and SHIV strains |
| 11478858 | 2001 | In vitro/Mechanistic | Journal of Molecular Biology | SIV gp41 binds membranes in both monomeric and trimeric states, informing the structural basis for fusion-inhibitor design |
EU Market Information
Enfuvirtide currently holds no marketing authorization in the EU dataset used for this evaluation (market status: not marketed; 0 licenses on record).
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted “indication” — SIV infection — is an animal research model rather than a human disease, so the supporting literature (mostly preclinical macaque studies of enfuvirtide-derived analogs, not enfuvirtide itself) does not translate into an actionable clinical development path. This is compounded by the absence of any EU marketing authorization and a blocking data gap on TFDA labeling.
To proceed, the following is needed:
- TFDA label warnings/contraindications (currently a blocking data gap, DG001)
- Confirmed mechanism of action documentation from DrugBank (DG002)
- Clarification of whether the intended human-relevant target is actually HIV-2 or drug-resistant HIV-1 (for which enfuvirtide-class fusion inhibitors have real clinical rationale), since SIV itself is not a treatable human condition
- Assessment of EU regulatory pathway given the drug’s current non-marketed status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.