Teriflunomide

證據等級: L5

預測適應症: 1 個

Teriflunomide: From Relapsing Multiple Sclerosis (Established Global Indication) to Relapsing-Remitting Multiple Sclerosis (TxGNN-Predicted)

One-Sentence Summary

Teriflunomide is an oral dihydroorotate dehydrogenase (DHODH) inhibitor already marketed globally (as Aubagio®) for relapsing forms of multiple sclerosis, though it is not currently registered in New Zealand. The TxGNN model predicts efficacy in Relapsing-Remitting Multiple Sclerosis, a prediction that is confirmatory rather than novel — it matches the drug's already-documented worldwide indication — and is backed by 28 clinical trials and 19 publications, including several completed Phase 3 RCTs.

Quick Overview

Item	Content
Original Indication	Not on file for New Zealand (drug unregistered); literature confirms teriflunomide (Aubagio®) is EU/globally approved for relapsing multiple sclerosis since 2013
Predicted New Indication	Relapsing-Remitting Multiple Sclerosis
TxGNN Prediction Score	99.24%
Evidence Level	L1 (≥2 completed Phase 3 RCTs)
New Zealand Market Status	Not Marketed (未上市)
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed DrugBank mechanism-of-action data was not returned in this evidence pack, but the literature evidence collected alongside the prediction fills the gap directly: teriflunomide "selectively and reversibly inhibits the mitochondrial enzyme dihydro-orotate dehydrogenase, with consequent inhibition of de novo pyrimidine synthesis and reduced lymphocyte proliferation" (PMID 31098896). This anti-proliferative effect on activated T- and B-lymphocytes is the accepted basis for its disease-modifying activity in autoimmune demyelinating disease.

Critically, the same literature set shows this is not an exploratory repurposing signal in the usual sense: PMID 26758290 states teriflunomide (Aubagio®) "has been licensed in the EU since August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS)." In other words, the TxGNN model's top prediction reproduces the drug's already-established, globally approved indication rather than identifying a genuinely new therapeutic use. This explains the unusually high score (99.24%) and the depth of supporting evidence — the model is correctly recovering known pharmacology, which is a useful sanity check on model validity, but should not be presented to stakeholders as a novel repurposing opportunity without that caveat.

The practical gap here is regulatory, not mechanistic: teriflunomide has zero New Zealand market authorizations on file, so the open question for this jurisdiction is registration and safety-label availability rather than efficacy rationale.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00134563	Phase 3	Completed	1088	Pivotal RCT: teriflunomide reduced relapse frequency and delayed disability accumulation (EDSS, MRI) vs. placebo
NCT00883337	Phase 3	Completed	324	TENERE: teriflunomide vs. interferon beta-1a — effectiveness (time to failure), relapse frequency, fatigue, safety
NCT00803049	Phase 3	Completed	742	Long-term extension documenting safety/tolerability of teriflunomide 7 mg and 14 mg, plus disability/relapse/MRI outcomes
NCT00228163	Phase 2	Completed	147	Long-term safety extension study; secondary long-term efficacy assessment
NCT02490982	N/A	Completed	106	Real-world observational effectiveness study in RRMS patients over ≥2 years
NCT03302442	N/A	Completed	3000	Real-world comparison of dimethyl fumarate vs. teriflunomide (French MS cohort), clinical + MRI outcomes
NCT03464448	N/A	Completed	30	Mechanistic study: regulatory B lymphocytes as mediators of teriflunomide's therapeutic effect
NCT02833714	N/A	Terminated	26	Mechanistic study on teriflunomide's effect on B-cell activation markers and cytokine secretion
NCT04129736	Phase 4	Completed	12	Pharmacokinetics: teriflunomide concentration in serum and cerebrospinal fluid
NCT03561402	N/A	Completed	24	Biomarkers associated with disease activity in teriflunomide-treated patients

Literature Evidence

PMID	Year	Type	Journal	Key Findings
32757523	2020	RCT	NEJM	Ofatumumab vs. teriflunomide head-to-head trial in relapsing MS
40202623	2025	RCT	NEJM	Tolebrutinib (BTK inhibitor) vs. teriflunomide in relapsing MS
36001711	2022	RCT	NEJM	Ublituximab vs. teriflunomide in relapsing MS
39307151	2024	RCT	Lancet Neurology	evolutionRMS1/2: evobrutinib vs. teriflunomide, phase 3 active-comparator trials
33779698	2021	RCT	JAMA Neurology	OPTIMUM: ponesimod vs. teriflunomide, first phase 3 head-to-head oral DMT comparison
38174776	2024	Systematic Review / Network Meta-analysis	Cochrane Database Syst Rev	Comparative efficacy of immunomodulators/immunosuppressants (incl. teriflunomide) for RRMS
31098896	2019	Review	Drugs	Comprehensive review of teriflunomide MOA (DHODH inhibition) and RCT/real-world efficacy in RRMS
26758290	2016	Review	CNS Drugs	Review of EU label, key efficacy/safety outcomes, and prescribing considerations for teriflunomide
33620411	2021	Review	JAMA	General MS diagnosis and treatment review, situates teriflunomide among DMTs
37691530	2023	Open-Label Extension	Mult Scler	ALITHIOS 4-year extension: ofatumumab shows superior efficacy/safety vs. teriflunomide over 2.5 years

New Zealand Market Information

Teriflunomide currently has no market authorizations on file in New Zealand (0 licenses; market status: not marketed). No product listing table can be produced from this evidence pack.

Safety Considerations

Please refer to the package insert for safety information. No warnings, contraindications, or drug interaction data were retrievable in this evidence pack — notably, TFDA package insert warnings/contraindications (DG001) are flagged as a blocking data gap that must be resolved before any safety pre-assessment (S1) can proceed.

Conclusion and Next Steps

Decision: Hold

Rationale: Clinical evidence is strong (L1, multiple completed Phase 3 RCTs) but two issues block progression: (1) the TFDA/Medsafe package insert with warnings and contraindications is a blocking data gap, so no safety pre-assessment can be completed; and (2) teriflunomide is unregistered in New Zealand (0 authorizations), and the predicted indication mirrors the drug's already-established global label rather than representing a genuinely novel repurposing target — this needs to be clarified before framing it as a repurposing candidate.

To proceed, the following is needed:

TFDA/Medsafe package insert (warnings, contraindications) to unblock S1 safety evaluation
Drug interaction (DDI) data — current query returned no results
Confirmation of New Zealand registration/import pathway and timeline for market entry
Explicit scoping decision on whether this candidate should be tracked as "novel repurposing" or reclassified as "market-access gap for an already-approved indication"
Disclaimer

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