Miltefosine
| 證據等級: L5 | 預測適應症: 4 個 |
目錄
Miltefosine: From Leishmaniasis to Diffuse Cutaneous Leishmaniasis
One-Sentence Summary
Miltefosine is an oral alkylphosphocholine antileishmanial, established for treating leishmaniasis (cutaneous, mucocutaneous, and visceral forms). The TxGNN model predicts it may also be effective for Diffuse Cutaneous Leishmaniasis (DCL), a rare and treatment-refractory subtype, with 0 registered clinical trials but 20 publications — including one Cochrane systematic review — currently supporting this direction. Several case reports show initial response followed by relapse, so durability of effect is unclear.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Leishmaniasis (cutaneous / mucocutaneous / visceral) — per known drug class use cited in evidence rationale; not separately confirmed by Taiwan regulatory license data |
| Predicted New Indication | Diffuse Cutaneous Leishmaniasis (DCL) |
| TxGNN Prediction Score | 99.72% |
| Evidence Level | L3 (observational studies / systematic review, no completed RCT) |
| Taiwan Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available (blocking data gap). Based on known information, miltefosine belongs to the alkylphosphocholine class of antileishmanial agents, acting by disrupting parasite cell membrane lipid metabolism and signal transduction; its efficacy in leishmaniasis (cutaneous, mucocutaneous, and visceral forms) is established.
Diffuse Cutaneous Leishmaniasis is a rare, chronic, multifocal form of the same disease that occurs in hosts with defective cell-mediated immunity against Leishmania, and is notoriously refractory to standard therapy. Extending an already-approved antileishmanial to this subtype is mechanistically plausible — it is the same pathogen genus, not a different disease. However, the literature consistently shows that while miltefosine can induce initial clinical response in DCL, relapse after treatment discontinuation is common, indicating the mechanism may control but not eliminate parasitic burden in this immunologically distinct presentation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32853410 | 2020 | Review (Cochrane systematic review) | Cochrane Database Syst Rev | Systematic review of interventions for American cutaneous/mucocutaneous leishmaniasis; evaluates miltefosine among alternatives to pentavalent antimonials |
| 26938448 | 2016 | Review (systematic review) | PLoS Negl Trop Dis | Systematic review of CL treatment for L. aethiopica, assessing miltefosine efficacy for severe/diffuse forms |
| 22050890 | 2011 | Review (clinical guideline) | J Dtsch Dermatol Ges | German joint working group review on CL/MCL diagnosis and therapy, discussing miltefosine as an oral option |
| 34048461 | 2021 | Cohort (prospective pilot study) | PLoS Negl Trop Dis | Pilot study of miltefosine for CL caused by L. aethiopica in Ethiopia; favorable side-effect profile vs. sodium stibogluconate |
| 28712122 | 2017 | Cohort (retrospective) | Trop Med Int Health | Clinical features and treatment response of CL in North-West Ethiopia, including diffuse and mucocutaneous forms |
| 41666471 | 2026 | Case report | Am J Trop Med Hyg | DCL patient with 60+ prior failed regimens over 22 years achieved complete remission after 180 days of miltefosine |
| 17441955 | 2007 | Case report | Br J Dermatol | DCL initially responds to miltefosine but relapses after treatment |
| 16796642 | 2006 | Case report | Int J Dermatol | Case report of DCL (31-year-old patient, disease since age 3) treated with miltefosine |
| 17172368 | 2006 | Case report | Am J Trop Med Hyg | New World DCL (L. mexicana) clears with miltefosine but relapses 2 months after stopping treatment |
| 25033218 | 2014 | In vitro/In vivo | PLoS Negl Trop Dis | Miltefosine susceptibility testing of L. amazonensis isolate from a DCL patient, informing alternative dosing strategies |
Taiwan Market Information
Miltefosine is not currently marketed in Taiwan (0 licenses on record); no NDA/authorization data is available.
Safety Considerations
Please refer to the package insert for safety information. TFDA warning/contraindication data and DDI data are currently unavailable (blocking data gap — TFDA label has not yet been sourced/parsed).
Conclusion and Next Steps
Decision: Hold
Rationale: No clinical trials have been conducted for the DCL indication specifically, and available evidence is limited to case reports, small cohorts, and one systematic review not focused on DCL relapse patterns — several case reports show relapse after treatment discontinuation, raising durability concerns. Additionally, the drug is unmarketed in Taiwan and the TFDA safety/label data gap (DG001, Blocking) prevents even an initial safety (S1) evaluation.
To proceed, the following is needed:
- TFDA label data (warnings, contraindications) — currently a blocking data gap
- Detailed mechanism of action (MOA) pharmacology data
- Prospective or controlled trial data specific to DCL (currently zero registered trials)
- Drug-drug interaction (DDI) data — currently not found
- Longer-term follow-up data addressing the relapse pattern seen across multiple case reports
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.