Teriflunomide

證據等級: L5

預測適應症: 1 個

Teriflunomide: From Established Use to TxGNN-Confirmed Relapsing-Remitting Multiple Sclerosis

One-Sentence Summary

Teriflunomide (DrugBank DB08880) is the active oral disease-modifying therapy marketed internationally as Aubagio®; structured original-indication data is not available in the local regulatory dataset, but published literature confirms it has been licensed in the EU/US for relapsing-remitting multiple sclerosis (RRMS) since 2013. The TxGNN model independently predicts RRMS as its top indication with a 99.24% confidence score — this is a case where the model recovers the drug's own established indication rather than surfacing a genuinely new one. The prediction is backed by 30 clinical trials (including multiple completed Phase 3 pivotal/comparator RCTs) and 20 publications, representing very strong evidence, though the drug is currently not marketed locally and a critical local safety-label data gap remains unresolved.

Quick Overview

Item	Content
Original Indication	Not documented in local regulatory data (drug not marketed locally); publicly known internationally as relapsing-remitting multiple sclerosis (Aubagio®, EU-approved since 2013)
Predicted New Indication	Relapsing-remitting multiple sclerosis
TxGNN Prediction Score	99.24%
Evidence Level	L1
Norway Market Status	✗ Not marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

The structured original_moa field is not populated, but the supporting literature is consistent and specific: teriflunomide is an oral, selective and reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH). By blocking de novo pyrimidine synthesis, it reduces proliferation and activation of rapidly dividing lymphocytes (both T- and B-cells), producing an anti-inflammatory, immunomodulatory effect (PMID 31098896, PMID 32757523).

The predicted indication — RRMS — is not a novel therapeutic area for teriflunomide; it is the drug's own established, globally approved use (marketed as Aubagio® in the EU since August 2013, per PMID 26758290, and used as the active comparator in numerous head-to-head Phase 3 trials against newer DMTs). This means the TxGNN score here should be interpreted as a validation signal — the model correctly recovers a well-known drug–disease relationship with very high confidence — rather than as a genuine repurposing opportunity.

Because the local (Taiwan/Norway) regulatory dataset shows zero licenses and no recorded original indication, this candidate's practical value is less about scientific novelty and more about flagging that teriflunomide currently has no local market authorization, despite robust global efficacy and safety data for RRMS.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00134563	Phase 3	Completed	1088	Pivotal RCT (TEMSO) — teriflunomide reduced relapse frequency and disability accumulation vs placebo in RMS
NCT00883337	Phase 3	Completed	324	TENERE study — compared teriflunomide (two doses) vs interferon beta-1a on time-to-failure and relapse frequency
NCT00803049	Phase 3	Completed	742	Long-term extension documenting safety/tolerability of teriflunomide 7 mg and 14 mg over time
NCT04788615	Phase 3	Completed	185	Ofatumumab vs physician-choice first-line DMT (incl. teriflunomide) in newly diagnosed RMS
NCT07189325	Phase 3	Not yet recruiting	250	Anti-CD20 maintenance vs de-escalation strategy in RRMS (teriflunomide-context trial)
NCT00228163	Phase 2	Completed	147	Long-term safety/efficacy extension of early Phase 2 teriflunomide study
NCT02490982	N/A	Completed	106	Observational effectiveness study of teriflunomide in real-world RRMS practice
NCT03464448	N/A	Completed	30	Mechanistic Phase 4 study on regulatory B-lymphocytes as mediators of teriflunomide's therapeutic effect
NCT04129736	Phase 4	Completed	12	Measured teriflunomide 14 mg concentration in serum and cerebrospinal fluid
NCT01881191	N/A	Completed	50	12-month MRI study of teriflunomide's effect on gray matter pathology

Literature Evidence

PMID	Year	Type	Journal	Key Findings
32757523	2020	RCT	NEJM	Ofatumumab vs teriflunomide head-to-head trial; describes teriflunomide's mechanism (pyrimidine synthesis inhibition, reduced T/B-cell activation)
40202623	2025	RCT	NEJM	Tolebrutinib (BTK inhibitor) vs teriflunomide in relapsing MS
36001711	2022	RCT	NEJM	Ublituximab vs teriflunomide in relapsing MS
33779698	2021	RCT	JAMA Neurology	OPTIMUM trial — ponesimod vs teriflunomide, first Phase 3 head-to-head of two oral DMTs
39307151	2024	RCT	Lancet Neurology	Evobrutinib (BTK inhibitor) vs teriflunomide, Phase 3 evolutionRMS1/2 trials
35266417	2022	RCT	Mult Scler	ASCLEPIOS I/II — ofatumumab vs teriflunomide in treatment-naive MS patients
38174776	2024	Systematic Review	Cochrane Database Syst Rev	Network meta-analysis of immunomodulators/immunosuppressants (incl. teriflunomide) for RRMS
31098896	2019	Review	Drugs	Comprehensive review of teriflunomide's mechanism, RCT and real-world evidence in RRMS
33620411	2021	Review	JAMA	General MS diagnosis and treatment review referencing teriflunomide as a first-line DMT
26758290	2016	Review	CNS Drugs	Review of EU Summary of Product Characteristics for teriflunomide, including safety outcomes

Norway Market Information

Teriflunomide currently holds no marketing authorization in the local (Taiwan/Norway) regulatory dataset (0 licenses recorded). No product, dosage form, or approved indication text is available to summarize.

Safety Considerations

Please refer to the package insert for safety information.

Note: A local regulatory label (TFDA warnings/contraindications) has not yet been retrieved and is flagged as a blocking data gap — see Conclusion below.

Conclusion and Next Steps

Decision: Hold

Rationale:

Global clinical evidence for teriflunomide in RRMS is extensive and strong (L1: multiple completed Phase 3 RCTs, extensive comparator literature, long-established international approval), but the predicted indication is essentially the drug's already-known primary indication rather than a novel repurposing signal — this candidate confirms the model rather than identifying new value.
More critically, a Blocking-severity data gap (DG001: TFDA label warnings/contraindications) prevents the candidate from entering the S1 safety pre-assessment stage, and the drug has zero local market authorizations.

To proceed, the following is needed:

Retrieve and parse the official local product label (warnings, contraindications) — required to clear the Blocking gap (DG001)
Obtain structured MOA confirmation from DrugBank (DG002)
Clarify whether a local market authorization filing is planned, given teriflunomide's established international approval (Aubagio®) for this same indication
Because this prediction largely reproduces a known indication, consider re-running TxGNN with known indications excluded to identify genuinely novel repurposing candidates for this drug
Disclaimer

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